4-amino-6-(heterocyclic)picolinates and 6-amino-2-(heterocyclic)pyrimidine-4-carboxylates and their use as herbicides

ABSTRACT

4-Amino-6-(heterocyclic)picolinic acids and their derivatives; 6-amino-2-(heterocyclic)pyrimidine-4-carboxylates and their derivatives; and methods of using the same as herbicides.

FIELD

The invention relates to herbicidal compounds and compositions and tomethods for controlling undesirable vegetation.

BACKGROUND

The occurrence of undesirable vegetation, e.g., weeds, is a constantproblem facing farmers in crops, pasture, and other settings. Weedscompete with crops and negatively impact crop yield. The use of chemicalherbicides is an important tool in controlling undesirable vegetation.

There remains a need for new chemical herbicides that offer a broaderspectrum of weed control, selectivity, minimal crop damage, storagestability, ease of handling, higher activity against weeds, and/or ameans to address herbicide-tolerance that develops with respect toherbicides currently in use.

SUMMARY OF THE INVENTION

Provided herein are compounds of Formula (I):

wherein

X is N or CY, wherein Y is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkoxy, C₁-C₃ alkylthioor C₁-C₃ haloalkylthio;

R¹ is OR^(1′) or NR^(1″)R^(1″′), wherein R^(1′) is hydrogen, C₁-C₈alkyl, or C₇-C₁₀ arylalkyl, and R^(1″) and R^(1″′) are independentlyhydrogen, C₁-C₁₂, alkyl, C₃-C₁₂ alkenyl, or C₃-C₁₂ alkynyl;

R² is halogen, C₁-C₁ alkyl, C₁-C₁ haloalkyl, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄ haloalkylthio, amino, C₁-C₄ alkylamino, C₂-C₄haloalkylamino, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl,cyano, or a group of the formula —CR¹⁷═CR¹⁸—SiR¹⁹R²⁰R²¹, wherein R¹⁷ ishydrogen, F, or Cl; R¹⁸ is hydrogen, F, Cl, C₁-C₄ alkyl, or C₁-C₄haloalkyl; and R¹⁹, R²⁰, and R²¹ are independently C₁-C₁₀ alkyl, C₃-C₆cycloalkyl, phenyl, substituted phenyl, C₁-C₁₀ alkoxy, or OH;

R³ and R⁴ are independently hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl,C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alknyl, formyl, C₁-C₃alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₆alkylcarbamyl, C₁-C₆ alkylsulfonyl, C₁-C₆ trialkylsilyl, C₁-C₆dialkylphosphonyl, or R³ and R⁴ taken together with N is a 5- or6-membered saturated ring, or R³ and R⁴ taken together represent═CR^(3′)(R^(4′)), wherein R^(3′) and R^(4′) are independently hydrogen,C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alknyl, C₁-C₆ alkoxy or C₁-C₆alkylamino, or, R^(3′) and R^(4′) taken together with ═C represent a 5-or 6-membered saturated ring;

A is one of groups A1 to A36

R⁵ , if applicable to the A group, is hydrogen, halogen, C₁-C₄ alkyl,C₁-C₄ haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino, C₂-C₄haloalkylamino, OH, or CN;

R⁶, R^(6′), and R^(6″), if applicable to the A group, are independentlyhydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, cyclopropyl,halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₃alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, amino,C₁-C₄ alkylamino or C₂-C₄ haloalkylamino, OH, CN, or NO₂;

R⁷ and R^(7′) are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy,C₁-C₃alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino, C₁-C₄haloalkylamino, or phenyl;

R⁸ is hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆haloalkenyl, C₃-C₆ alknyl, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkylcarbamyl, C₁-C₆alkylsulfonyl, C₁-C₆ trialkylsilyl, or phenyl;

or an N-oxide or agriculturally acceptable salt thereof.

Also provided are methods of controlling undesirable vegetationcomprising (a) contacting the undesirable vegetation or area adjacent tothe undesirable vegetation or (b) pre-emergently contacting soil orwater a herbicidally effective amount of at least one compound ofFormula (I) or agriculturally acceptable derivative thereof.

Also provided are novel precursors of Formula (II):

wherein:

R⁷ and R^(7′) are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino, C₂-C₄haloalkylamino, or phenyl;

R⁸ is hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆haloalkenyl, C₃-C₆ alknyl, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkylcarbamyl, C₁-C₆alkylsulfonyl, C₁-C₆ trialkylsilyl, or phenyl;

Z is B(OR²²)₂, BF₃M, or Sn(R²³)₃, wherein each R²² is independentlyhydrogen or C₁-C₄ alkyl, or the two OR²² moieties combine to form—O—C(CH₃)₂—C(CH₃)₂—O— or —O—CH₂—C(CH₃)₂—CH₂—O—; M is a metal cation,e.g. sodium or potassium, and R²³ is C ₁-C₄ alkyl; provided thefollowing compound is excluded:

DETAILED DESCRIPTION Definitions

As used herein, herbicide and herbicidal active ingredient mean acompound that controls undesirable vegetation when applied in anappropriate amount.

As used herein, control of or controlling undesirable vegetation meanskilling or preventing the vegetation, or causing some other adversemodifying effect to the vegetation e.g., deviations from natural growthor development, regulation, desiccation, retardation, and the like.

As used herein, a herbicidally effective or vegetation controllingamount is an amount of herbicidal active ingredient the application ofwhich controls the relevant undesirable vegetation.

As used herein, applying an herbicide or herbicidal composition meansdelivering it directly to the targeted vegetation or to the locusthereof or to the area where control of undesired vegetation is desired.Methods of application include, but are not limited to pre-emergentlycontacting soil or water, post-emergently contacting the undesirablevegetation or area adjacent to the undesirable vegetation.

As used herein, plants and vegetation include, but are not limited to,dormant seeds, germinant seeds, emerging seedlings, plants emerging fromvegetative propagules, immature vegetation, and established vegetation.

As used herein, agriculturally acceptable salts and esters refer tosalts and esters that exhibit herbicidal activity, or that are or can beconverted in plants, water, or soil to the referenced herbicide.Exemplary agriculturally acceptable esters are those that are or can byhydrolyzed, oxidized, metabolized, or otherwise converted, e.g., inplants, water, or soil, to the corresponding carboxylic acid which,depending on the pH, may be in the dissociated or undissociated form.

Suitable salts include those derived from alkali or alkaline earthmetals and those derived from ammonia and amines Preferred cationsinclude sodium, potassium, magnesium, and aminium cations of theformula:

R¹³R¹⁴R¹⁵R¹⁶N⁺

wherein R¹³, R¹⁴, R¹⁵ and R¹⁶ each, independently represents hydrogen orC₁-C₁₂ alkyl, C₃-C₁₂ alkenyl or C₃-C₁₂ alkynyl, each of which isoptionally substituted by one or more hydroxy, C₁-C₄ alkoxy, C₁-C₄alkylthio or phenyl groups, provided that R¹³, R¹⁴, R¹⁵ and R¹⁶ aresterically compatible. Additionally, any two R¹³, R¹⁴, R¹⁵ and R¹⁶together may represent an aliphatic difunctional moiety containing oneto twelve carbon atoms and up to two oxygen or sulfur atoms. Salts ofthe compounds of Formula I can be prepared by treatment of compounds ofFormula I with a metal hydroxide, such as sodium hydroxide, with anamine, such as ammonia, trimethylamine, diethanolamine,2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine,cyclododecylamine, or benzylamine or with a tetraalkylammoniumhydroxide, such as tetramethylammonium hydroxide or choline hydroxide.Amine salts are often preferred forms of the compounds of Formula Ibecause they are water-soluble and lend themselves to the preparation ofdesirable aqueous based herbicidal compositions.

Compounds of the formula (I) include N-oxides. Pyridine N-oxides can beobtained by oxidation of the corresponding pyridines. Suitable oxidationmethods are described, for example, in Houben-Weyl, Methoden derorganischen Chemie [Methods in organic chemistry], expanded andsubsequent volumes to the 4th edition, volume E 7b, p. 565 f.

As used herein, unless otherwise specified, acyl refers to formyl, C₁-C₃alkylcarbonyl, and C₁-C₃ haloalkylcarbonyl. C₁-C₆ acyl refers to formyl,C₁-C₅ alkylcarbonyl, and C₁-C₅ haloalkylcarbonyl (the group contains atotal of 1 to 6 carbon atoms).

As used herein, alkyl refers to saturated, straight-chained or branchedsaturated hydrocarbon moieties. Unless otherwise specified, C₁-C₁₀ alkylgroups are intended. Examples include methyl, ethyl, propyl,1-methyl-ethyl, butyl, 1-methyl-propyl, 2-methyl-propyl,1,1-dimethyl-ethyl, pentyl, 1-methyl-butyl, 2-methyl-butyl,3-methyl-butyl, 2,2-dimethyl-propyl, 1-ethyl-propyl, hexyl,1,1-dimethyl-propyl, 1,2-dimethyl-propyl, 1-methyl-pentyl,2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, 1,1-dimethyl-butyl,1,2-dimethyl-butyl, 1,3-dimethyl-butyl, 2,2-dimethyl-butyl,2,3-dimethyl-butyl, 3,3-dimethyl-butyl, 1-ethyl-butyl, 2-ethyl-butyl,1,1,2-trimethyl-propyl, 1,2,2-trimethyl-propyl, 1-ethyl-1-methyl-propyl,and 1-ethyl-2-methyl-propyl.

As used herein, “haloalkyl” refers to straight-chained or branched alkylgroups, where in these groups the hydrogen atoms may partially orentirely be substituted with halogen atoms. Unless otherwise specified,C₁-C₈ groups are intended. Examples include chloromethyl, bromomethyl,dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl,trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl,chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl,2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,2-chloro-2-fluoroethyl, 2-chloro-2-difluoroethyl,2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and1,1,1-trifluoroprop-2-yl.

As used herein, alkenyl refers to unsaturated, straight-chained, orbranched hydrocarbon moieties containing a double bond. Unless otherwisespecified, C₂-C₈ alkynyl are intended. Alkynyl groups may contain morethan one unsaturated bond. Examples include ethenyl, 1-propenyl,2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl,1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl,2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl,1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl,1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl,1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl,1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl,1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl,4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl,3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl,2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl,1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl,4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl,1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl,1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl,2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl,2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl,1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl,1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl,1-ethyl-2-methyl-1-propenyl, and 1-ethyl-2-methyl-2-propenyl. Vinylrefers to a group having the structure —CH═CH₂, 1-propenyl refers to agroup with the structure —CH═CH—CH₃; and 2-propenyl refers to a groupwith the structure —CH₂—CH═CH₂.

As used herein, alkynyl represents straight-chained or branchedhydrocarbon moieties containing a triple bond. Unless otherwisespecified, C₂-C₈ alkynyl groups are intended. Alkynyl groups may containmore than one unsaturated bond. Examples include C₂-C₆-alkyynyl, such asethynyl, 1-propynyl, 2-propynyl (or propargyl), 1-butyynyl, 2-butynyl,3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl,4-pentynyl, 3-methyl-1-butynyl, 1-methyl-2-butynyl, 1-methyl-3-butinyul,2-methyl-3-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl,1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl,3-methyl-1-pentynyl, 4-methyl-1-pentynyl, 1-methyl-2-pentynyl,4-methyl-2-pentynyl, 1-methyl-3-pentynyl, 2-methyl-3-pentynyl,1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl,1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl,2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl,1-ethyl-3-butynyl, 2-ethyl-3-butynyl, and 1-ethyl-1-methyl-2-propynyl.

As used herein, alkoxy refers to a group of the formula R—O—, where R isalkyl as defined above. Unless otherwise specified, alkoxy groupswherein R is a C₁-C₈ alkyl group are intended. Examples include methoxy,ethoxy, propoxy, 1-methyl-ethoxy, butoxy, 1-methyl-propoxy,2-methyl-propoxy, 1,1-dimethyl-ethoxy, pentoxy, 1-methyl-butyloxy,2-methyl-butoxy, 3-methyl-butoxy, 2,2-di-methyl-propoxy,1-ethyl-propoxy, hexoxy, 1,1-dimethyl-propoxy, 1,2-dimethyl-propoxy,1-methyl-pentoxy, 2-methyl-pentoxy, 3-methyl-pentoxy, 4-methyl-penoxy,1,1-dimethyl-butoxy, 1,2-dimethyl-butoxy, 1,3-dimethyl-butoxy,2,2-dimethyl-butoxy, 2,3-dimethyl-butoxy, 3,3-dimethyl-butoxy,1-ethyl-butoxy, 2-ethylbutoxy, 1,1,2-trimethyl-propoxy,1,2,2-trimethyl-propoxy, 1-ethyl-1-methyl-propoxy, and1-ethyl-2-methyl-propoxy.

As used herein, haloalkoxy refers to a group of the formula R—O—, whereR is haloalkyl as defined above. Unless otherwise specified, haloalkoxygroups wherein R is a C₁-C₈ alkyl group are intended. Examples includechloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy,fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy,dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy,1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy,2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy,2-chloro,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy,2,2,2-trichloroethoxy, pentafluoroethoxy, and 1,1,1-trifluoroprop-2-oxy.

As used herein, alkylthio refers to a group of the formula R—S— where Ris alkyl as defined above. Unless otherwise specified, alkylthio groupswherein R is a C₁-C₈ alkyl group are intended. Examples includemethylthio, ethylthio, propylthio, 1-methylethylthio, butylthio,1-methyl-propylthio, 2-methylpropylthio, 1,1-dimethylethylthio,pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio,2,2-dio-methylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2-dimethyl propylthio, 1-methylpentylthio,2-methylpentylthio, 3-methyl-pentylthio, 4-methyl-pentylthio,1,1-dimethyl butylthio, 1,2-dimethyl-butylthio, 1,3-dimethyl-butylthio,2,2-dimethyl butylthio, 2,3-dimethyl butylthio, 3,3-dimethylbutylthio,1-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethyl propylthio,1,2,2-trimethyl propylthio, 1-ethyl-1-methyl propylthio, and1-ethyl-2-methylpropylthio.

As used herein, haloalkylthio refers to an alkylthio group as definedabove wherein the carbon atoms are partially or entirely substitutedwith halogen atoms. Unless otherwise specified, haloalkylthio groupswherein R is a C₁-C₈ alkyl group are intended. Examples includechloromethylthio, bromomethylthio, dichloromethylthio,trichloromethylthio, fluoromethylthio, difluoromethylthio,trifluoromethylthio, chlorofluoromethylthio, dichlorofluoro-methylthio,chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethylthio,1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio,2,2,2-trifluoroethylthio, 2-chloro-2-fluoroethylthio,2-chloro-2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio,2,2,2-trichloroethylthio, pentafluoroethylthio, and1,1,1-trifluoroprop-2-ylthio.

As used herein, aryl, as well as derivative terms such as aryloxy,refers to a phenyl, indanyl or naphthyl group with phenyl beingpreferred. The term “heteroaryl”, as well as derivative terms such as“heteroaryloxy”, refers to a 5- or 6-membered aromatic ring containingone or more heteroatoms, viz., N, O or S; these heteroaromatic rings maybe fused to other aromatic systems. The aryl or heteroaryl substituentsmay be unsubstituted or substituted with one or more substituentsselected from halogen, hydroxy, nitro, cyano, formyl, C₁-C₆ alkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₁-C₆ alkoxy, C₁-C₆ haloalkyl, C₁-C₆ haloalkoxy,C₁-C₆ acyl, C₁-C₆ alkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ alkylsulfonyl,C₁-C₆ alkoxycarbonyl, C₁-C₆ carbamoyl, hydroxycarbonyl, C₁-C₆alkylcarbonyl, aminocarbonyl, C₁-C₆ alkylaminocarbonyl, C₁-C₆dialkylaminocarbonyl, provided that the substituents are stericallycompatible and the rules of chemical bonding and strain energy aresatisfied. Preferred substituents include halogen, C₁-C₂ alkyl and C₁-C₂haloalkyl.

As used herein alkylcarbonyl refers to an alkyl group bonded to acarbonyl group. C₁-C₃ alkylcarbonyl and C₁-C₃ haloalkylcarbonyl refer togroups wherein a C₁-C₃ alkyl group is bonded to a carbonyl group (thegroup contains a total of 2 to 4 carbon atoms).

As used herein, alkoxycarbonyl refers to a group of the formula

wherein R is alkyl.

As used herein, arylalkyl refers to an alkyl group substituted with anaryl group. C₇-C₁₀ arylalkyl refers to a group wherein the total numberof carbon atoms in the group is 7 to 10.

As used herein alkylamino refers to an amino group substituted with oneor two alkyl groups, which may be the same or different.

As used herein haloalkylamino refers to an alkylamino group wherein thealkyl carbon atoms are partially or entirely substituted with halogenatoms.

As used herein, C₁-C₆ alkylaminocarbonyl refers to a group of theformula RNHC(O)— wherein R is C₁-C₆ alkyl, and C₁-C₆dialkylaminocarbonyl refers to a group of the formula R₂NC(O)— whereineach R is independently C₁-C₆ alkyl.

As used herein alkylcarbamyl refers to a carbamyl group substituted onthe nitrogen with an alkyl group.

As used herein alkylsulfonyl refers to a group of the formula

where R is alkyl

As used herein carbamyl (also referred to as carbamoyl andaminocarbonyl) refers to a group of the formula

As used herein dialkylphosponyl refers to a group of the formula

where R is independently alkyl in each occurrence.

As used herein, C₁-C₆ trialkylsilyl refers to a group of the formula—SiR₃ wherein each R is independently a C₁-C₆ alkyl group (the groupcontains a total of 3 to 18 carbon atoms).

As used herein Me refers to a methyl group; OMe refers to a methoxygroup; i-Pr refers to an isopropyl group.

As used herein, the term “halogen” including derivative terms such as“halo” refers to fluorine, chlorine, bromine and iodine.

As used herein, plants and vegetation include, but are not limited to,germinant seeds, emerging seedlings, plants emerging from vegetativepropagules, immature vegetation, and established vegetation.

Compounds of Formula (I)

The invention provides compounds of Formula (I) as defined above andN-oxides and agriculturally acceptable salts thereof.

In some embodiments, the compound is the carboxylic acid or anagriculturally acceptable ester or salt. In some embodiments, thecompound is the carboxylic acid or its methyl ester.

In some embodiments:

A is one of groups A1 to A20;

R¹ is OR^(1′), wherein R^(1′) is hydrogen or C₁-C₄ alkyl;

R² is chlorine;

R³ and R⁴ are hydrogen;

X is N, CH, CF, CCl, or CBr;

R⁵ is hydrogen, halogen, OH, NH2, CN, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃alkylamino, or cyclopropyl;

R⁶, R^(6′), and R^(6″) are independently hydrogen, halogen, OH, NH₂, CN,C₁-C₃ alkyl, C₁-C₃ alkoxy, cyclopropyl, or vinyl;

R⁷ and R^(7′) are independently hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃alkoxy, C₁-C₃ alkylthio, cyclopropyl, or C₁-C₃ alkylamino, or phenyl;and

R⁸ is hydrogen, C₁-C₃ alkyl, phenyl, or C₁-C₃ alkylcarbonyl.

In some embodiments, R¹ is OR^(1′), wherein R^(1′) is hydrogen, C₁-C₈alkyl, or C₇-C₁₀ arylalkyl. In some embodiments, R^(1′) is hydrogen orC₁-C₈ alkyl. In some embodiments, R^(1′) is hydrogen.

In some embodiments, R² is halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₄alkynyl, C₂-C₄-alkenyl, C₂-C₄ haloalkenyl, or C₁-C₄-alkoxy, or C₁-C₄haloalkoxy. In some embodiments, R² is halogen, C₂-C₄-alkenyl, C₂-C₄haloalkenyl, or C₁-C₄-alkoxy. In some embodiments, R² is halogen. Insome embodiements, R² is C₂-C₄-alkenyl or C₂-C₄ haloalkenyl. In someembodiments, R² is C₁-C₄ alkoxy. In some embodiments, R² is Cl, OMe,vinyl, or 1-propenyl. In some embodiments, R² is Cl. In someembodiments, R² is OMe. In some embodiments, R² is vinyl or 1-propenyl.

In some embodiments, R³ and R⁴ are independently hydrogen, C₁-C₆ alkyl,C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alknyl, formyl,C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl,C₁-C₆ alkylcarbamyl, or R³ and R⁴ taken together represent═CR^(3′)(R^(4′)), wherein R^(3′) and R^(4′) are independently hydrogen,C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alknyl, C₁-C₆ alkoxy, or C₁-C₆alkylamino In some embodiments, R³ and R⁴ are independently hydrogen,C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, formyl,C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, or R³ and R⁴ takentogether represent ═CR^(3′)(R^(4′)), wherein R^(3′) and R^(4′) areindependently hydrogen, C₁-C₆ alkyl, C₁-C₆ alkoxy or C₁-C₆ alkylamino Insome embodiments, R^(3′) and R^(4′) are independently hydrogen, C₁-C₆alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, formyl, C₁-C₃alkylcarbonyl, or C₁-C₃ haloalkylcarbonyl. In some embodiments, at leastone of R³ and R⁴ are hydrogen. In some embodiments, R³ and R⁴ are bothhydrogen.

In some embodiments, X is N, CH or CF. In some embodiments, X is N. Insome embodiments, X is CH. In some embodiments, X is CF.

In some embodiments, A is A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11,A12, A13, A14, A15, A16, A17, A18, A19, or A20.

In some embodiments, A is one of A21, A22, A23, A24, A25, A26, A27, A28,A29, A30, A31, A32, A33, A34, A35, and A36.

In some embodiments, A is one of groups A1, A2, A3, A7, A8, A9, A10,A13, A14, and A15. In some embodiments, A is one of groups A1, A2, A3,A13, A14, and A15. In some embodiments, A is one of groups A13, A14, andA15. In some embodiments, A is A15.

In some embodiments, R⁵ is hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃haloalkylthio, or amino In some embodiments, R⁵ is hydrogen, halogen,C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, or aminoIn some embodiments, R⁵ is hydrogen, halogen, C₁-C₄ alkyl or C₁-C₄alkoxy. In some embodiments, R⁵ is hydrogen or F. In some embodiments,R⁵ is hydrogen. In some embodiments, R⁵ is F.

In some embodiments, R⁶ is hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄haloalkyl, C₁-C₃ alkoxy, or C₁-C₃ haloalkoxy. In some embodiments, R⁶ ishydrogen or fluorine. In some embodiments, R⁶ is hydrogen. In someembodiments, R⁶ is fluorine.

In some embodiments, R^(6′) is hydrogen or halogen. In some embodiments,R^(6′) is hydrogen, F, or Cl. In some embodiments, R^(6′) is hydrogen orF. In some embodiments, R^(6′) is hydrogen.

In some embodiments, R^(6″) is hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄haloalkyl, cyclopropyl, C₂-C₄ alkynyl, CN, or NO₂. In some embodiments,R^(6″) is hydrogen. In some embodiments, R^(6″) is halogen. In someembodiments, R^(6″) is C₁-C₄ alkyl. In some embodiments, R^(6″) is C₁-C₄haloalkyl. In some embodiments, R^(6″) is cyclopropyl. In someembodiments, R^(6″) is C₂-C₄ alkynyl. In some embodiments, R^(6″) is CN.In some embodiments, R^(6″) is NO₂.

In some embodiments:

-   -   R² is halogen, C₂-C₄-alkenyl, C₂-C₄ haloalkenyl, or        C₁-C₄-alkoxy;    -   R³ and R⁴ are both hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is halogen;    -   R³ and R⁴ are both hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is C₂-C₄-alkenyl or C₂-C₄ haloalkenyl;    -   R³ and R⁴ are both hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is C₁-C₄-alkoxy;    -   R³ and R⁴ are both hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is halogen, C₂-C₄-alkenyl, C₂-C₄ haloalkenyl, or        C₁-C₄-alkoxy;    -   R³ and R⁴ are both hydrogen;    -   X is N, CH, or CF;    -   R⁵ is hydrogen or F;    -   R⁶ is hydrogen or F;    -   R^(6′) is hydrogen;    -   R^(6″), if applicable to the relevant A group, is hydrogen or        halogen; and    -   R⁷ and R^(7′), if applicable to the relevant A group, are        independently hydrogen or halogen.

In some embodiments:

-   -   R² is halogen, C₁-C₄-alkoxy, or C₂-C₄-alkenyl;    -   R³ and R⁴ are hydrogen;    -   X is N, CH, or CF; and    -   A is one of groups A1 to A20;

In some embodiments:

-   -   R² is chlorine;    -   R³ and R⁴ are hydrogen;    -   X is N, CH, or CF;    -   A is one of groups A1 to A20;    -   R⁵ is hydrogen or F;    -   R⁶ and R^(6′) are independently hydrogen or F; and    -   R⁷ and R^(7′), if applicable to the relevant A group, are        independently hydrogen, halogen, C₁-C₄ alkyl, or C₁-C₄        haloalkyl.

In some embodiments:

-   -   R² is chlorine, methoxy, vinyl, or 1-propenyl;    -   R³ and R⁴ are hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is chlorine;    -   R³ and R⁴ are hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is vinyl or 1-propenyl;    -   R³ and R⁴ are hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is methoxy;    -   R³ and R⁴ are hydrogen; and    -   X is N, CH, or CF.

In some embodiments:

-   -   R² is chlorine;    -   R³ and R⁴ are hydrogen; and    -   X is N.

In some embodiments:

-   -   R² is chlorine;    -   R³ and R⁴ are hydrogen; and    -   X is CH.

In some embodiments:

-   -   R² is chlorine;    -   R³ and R⁴ are hydrogen; and    -   X is CF.

In some embodiments:

-   -   R² is chlorine;    -   R³ and R⁴ are hydrogen;    -   X is CF;    -   A is one of A1, A2, A3, A7, A8, A9, A10, A13, A14, or A15;    -   R⁵ is F; and    -   R⁶ is H.

In some embodiments:

-   -   R² is chlorine, methoxy, vinyl, or 1-propenyl;    -   R³ and R⁴ are hydrogen;    -   X is N, CH, or CF; and    -   A is one of A21-A36.

In some embodiments:

-   -   R² is chlorine, methoxy, vinyl, or 1-propenyl;    -   R³ and R⁴ are hydrogen;    -   X is CF; and    -   A is one of

wherein R⁵ is hydrogen or F.

In some embodiments:

-   -   R² is chlorine, methoxy, vinyl, or 1-propenyl;    -   R³ and R⁴ are hydrogen;    -   X is N, CH, or CF; and    -   A is

where R⁵ is hydrogen or F.

In some embodiments:

-   -   R² is chlorine, methoxy, vinyl, or 1-propenyl;    -   R³ and R⁴ are hydrogen;    -   X is N, CH, or CF; and    -   A is

In some embodiments:

-   -   R² is chlorine, methoxy, vinyl, or 1-propenyl;    -   R³ and R⁴ are hydrogen;    -   X is CF; and    -   A is

It is particularly noteworthy that compounds of Formula (I) wherein Ais, e.g. A15, exhibit a significant increase in activity when X is CF.This is demonstrated by comparing the activity of Compounds 1.21 and1.22 (wherein X is CH) with that of 1.08 and 1.09 (wherein X is CF). Itis also demonstrated by comparing the activity of Compounds 1.23 and1.24 (wherein X is CH) with that of Compounds 1.15 and 1.16 (wherein Xis CF). The increased activity is further enhanced when R⁵ is F.

Exemplary Compounds

The following Tables 1-9 describe exemplary compounds of Formula (I′)

Table 10 sets forth the structure, appearance, preparation method, andprecursor(s) used in synthesis of the exemplary compounds. Table 11 setsforth physical data for each of the exemplary compounds.

Blank spaces in compound tables herein indicate hydrogen, or that forthe A group indicated in a particular row the column in which the blankoccurs is not relevant

TABLE 1 Compounds of Formula (I′) with indolyl tails A3

A15

A27

A28

C. No. R^(1′) R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 1.01 H Cl CF A03Me 1.02 Me Cl CF A03 1.03 Me Cl CF A03 Me 1.04 H Cl CF A03 1.05 Me ClCCl A15 1.06 H Cl CCl A15 1.07 Me Cl CCl A15 F 1.08 Me Cl CF A15 1.09 HCl CF A15 1.10 Me Cl CF A15 Me 1.11 H Cl CF A15 Me 1.12 Me Cl CF A15 FSi(i-Pr)₃ 1.13 Me Cl CF A15 F 1.14 H Cl CF A15 F 1.15 Me Cl CF A15 F1.16 H Cl CF A15 F 1.17 H OMe CF A15 F 1.18 Me vinyl CF A15 F 1.19 Hvinyl CF A15 F 1.20 Me OMe CF A15 F 1.21 Me Cl CH A15 1.22 H Cl CH A151.23 Me Cl CH A15 F 1.24 H Cl CH A15 F 1.25 Me Cl CH A15 F 1.26 H Cl CHA15 F 1.27 Me Cl CH A15 F F 1.28 Me Cl CMe A15 1.29 H Cl CMe A15 1.30 MeCl N A15 1.31 Me Cl N A15 F 1.32 Me OMe N A15 1.33 H OMe N A15 1.34 MeOMe N A15 F 1.35 H OMe N A15 F 1.36 Me OMe N A15 F 1.37 H OMe N A15 F1.38 Me vinyl N A15 F 1.39 H vinyl N A15 F 1.40 Me Cl CF A27 1.41 Me ClCF A27 Me 1.42 H Cl CF A27 Me 1.43 Me Cl CF A27 Cl 1.44 Me Cl CH A27 Cl1.45 Me OMe N A27 Cl 1.46 Me Cl CF A28 Cl 1.47 Me Cl CF A28 1.48 H Cl CFA28 1.49 Me Cl CH A28 Cl 1.50 Me OMe N A28 Cl A is A3, A15, A27, or A28

TABLE 2 Compounds of Formula (I′) with bernzofuranyl tails A1

A13

A21

A22

C. No. R^(1′) R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 2.01 Me Cl CF A012.02 H Cl CF A01 2.03 Me Cl CH A01 2.04 Me Cl CH A01 F 2.05 Me OMe N A01F 2.06 Me OMe N A01 2.07 Me Cl CF A13 2.08 H Cl CF A13 2.09 Me Cl CF A13F 2.10 Me Cl CF A13 F 2.11 Me Cl CH A13 F 2.12 Me Cl CH A13 F 2.13 MeOMe N A13 F 2.14 Me OMe N A13 F 2.15 Me Cl CF A21 2.16 Me Cl CF A21 Cl2.17 H Cl CF A21 2.18 H Cl CF A21 Cl 2.19 Me Cl CH A21 Cl 2.20 Me Cl NA21 Cl 2.21 Me OMe N A21 Cl 2.22 H OMe N A21 Cl 2.23 H Cl N A21 Cl 2.24Me Cl CF A22 Cl 2.25 Me Cl CH A22 Cl 2.26 Me OMe N A22 Cl A is A1, A13,A21, or A22

TABLE 3 Compounds of Formula (I′) with benzothiofuranyl tails A2

A14

A23

A24

A is A2, A14, A23, or A24: C. No. R^(1′) R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷R^(7′) R⁸ 3.01 Me Cl CCl A02 3.02 H Cl CCl A02 3.03 Me Cl CF A02 3.04 HCl CF A02 3.05 Me Cl CH A02 3.06 Me Cl CMe A02 3.07 H Cl CMe A02 3.08 MeOMe N A02 3.09 H OMe N A02 3.10 Me Cl CCl A14 3.11 H Cl CCl A14 3.12 MeCl CF A14 3.13 H Cl CF A14 3.14 Me Cl CF A14 F 3.15 Me Cl CH A14 3.16 HCl CH A14 3.17 Me Cl CH A14 F 3.18 Me Cl CMe A14 3.19 H Cl CMe A14 3.20Me OMe N A14 3.21 H OMe N A14 3.22 Me OMe N A14 F 3.23 Me Cl CF A23 3.24Me Cl CF A24 3.25 H Cl CF A24 3.26 Me Cl CF A24 Br 3.27 Me Cl CH A24

TABLE 4 Compounds of Formula (I′) with IH-indazolyl tails C. No. R^(1′)R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 4.01 Me Cl CF A06 4.02 H Cl CFA06 4.03 Me Cl CF A06 Me 4.04 H Cl CF A06 Me 4.05 Me Cl CF A18 4.06 H ClCF A18 4.07 Me Cl CF A18 Me 4.08 H Cl CF A18 Me 4.09 Me Cl CH A18 4.10Me Cl CF A25 Me 4.11 H Cl CF A25 Me 4.12 Me Cl CF A25 4.13 Me Cl CF A26A is one of groups A6, A18, A25, and A26:  

 

 

 

TABLE 5 Compounds of Formula (I′) with benzoxazolyl tails C. No. R^(1′)R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 5.01 Me Cl CF A09 A is A7, A9,A29, or A30:  

 

 

 

TABLE 6 Compounds of Formula (I′) with benzothiazolyl tails C. No.R^(1′) R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 6.01 Me Cl CF A08 6.02 HCl CF A08 A is A8, A10, A31, or A32:  

 

 

 

TABLE 7 Compounds of Formula (I′) with 1H-benzimidazolyl tails C. No.R^(1′) R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 7.01 Me Cl CF A12 7.02 MeCl CF A12 Me 7.03 H Cl CF A12 Me A is one of groups A11 and A12:  

 

TABLE 8 Compounds of Formula (I′) with indoxazinyl tails C. No. R^(1′)R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 8.01 Me Cl CF A16 NMe₂ A is A4,A16, A33, or A34:  

 

 

 

TABLE 9 Compounds of Formula (I′) with 1H-benzotriazolyl tails C. No.R^(1′) R² X A R⁵ R⁶ R^(6′) R^(6″) R⁷ R^(7′) R⁸ 9.01 Me Cl CH A20 A isA19 or A20:  

 

Methods of Preparing the Compounds

Exemplary procedures to synthesize the compounds of Formula (I) areprovided below.

The 4-amino-6-(heterocyclic)picolinic acids of Formula (I) can beprepared in a number of ways. As depicted in Scheme I, the4-amino-6-chloropicolinates of Formula (II) can be converted to the4-amino-6-substituted-picolinates of Formula (III), wherein Ar is asherein defined, via Suzuki coupling with a boronic acid or ester, in thepresence of a base, such as potassium fluoride, and a catalyst, such asbis(triphenylphosphine)-palladium(II) dichloride, in a polar, proticsolvent mixture, such as acetonitrile-water, at a temperature, such as110° C., e.g., in a microwave reactor (reaction a₁).4-Amino-6-substituted-picolinates of Formula (III) can be transformedinto the 5-iodo-4-amino-6-substituted-picolinates of Formula (IV) via areaction with iodinating reagents, such as periodic acid and iodine, ina polar, protic solvent, such as methyl alcohol (reaction b₁). Stillecoupling of the 5-iodo-4-amino-6-substituted-picolinates of Formula (IV)with a stannane, such as tetramethyltin, in the presence of a catalyst,such as bis(triphenylphosphine)-palladium(II) dichloride, in anon-reactive solvent, such as 1,2-dichloroethane, at a temperature, suchas 120-130° C., e.g., in a microwave reactor, provides5-(substituted)-4-amino-6-substituted-picolinates of Formula (I-A),wherein Z₁ is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio(reaction c₁).

Alternatively, 4-amino-6-chloropicolinates of Formula (II) can betransformed to the 5-iodo-4-amino-6-chloropicolinates of Formula (V) viaa reaction with iodinating reagents, such as periodic acid and iodine,in a polar, protic solvent, such as methyl alcohol (reaction b₂). Stillecoupling of the 5-iodo-4-amino-6-chloropicolinates of Formula (V) with astannane, such as tetramethyltin, in the presence of a catalyst, such asbis(triphenylphosphine)-palladium(II) dichloride, in a non-reactivesolvent, such as 1,2-dichloroethane, at a temperature, such as 120-130°C., e.g., in a microwave reactor, provides5-(substituted)-4-amino-6-chloropicolinates of Formula (VI), wherein Z₁is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio (reaction c₂). The5-substituted-4-amino-6-chloropicolinates of Formula (VI) can beconverted to the 5-substituted-4-amino-6-substituted-picolinates ofFormula (I-A), wherein Ar is as herein defined, via Suzuki coupling witha boronic acid or ester, in the presence of a base, such as potassiumfluoride, and a catalyst, such as bis(triphenylphosphine)-palladium(II)dichloride, in a polar, protic solvent mixture, such asacetonitrile-water, at a temperature, such as 110° C., e.g., in amicrowave reactor (reaction a₂).

As depicted in Scheme II, the 4,5,6-trichloropicolinate of Formula (VII)can be converted to the corresponding isopropyl ester of Formula (VIII),via a reaction with isopropyl alcohol and concentrated sulfuric acid,e.g., at reflux temperature under Dean-Stark conditions (reaction d).The isopropyl ester of Formula (VIII) can be reacted with a fluoride ionsource, such as cesium fluoride, in a polar, aprotic solvent, such asdimethyl sulfoxide, at a temperature, such as 80° C., under Dean-Starkconditions, to yield the isopropyl 4,5,6-trifluoropicolinate of Formula(IX) (reaction e). The isopropyl 4,5,6-trifluoropicolinate of Formula(IX) can be aminated with a nitrogen source, such as ammonia, in apolar, aprotic solvent, such as dimethyl sulfoxide, to produce a4-amino-5,6-difluoropicolinate of Formula (X) (reaction f). The fluorosubstituent in the 6-position of the 4-amino-5,6-difluoropicolinate ofFormula (X) can be exchanged with a chloro substituent by treatment witha chloride source, such as hydrogen chloride, e.g., in dioxane, in aParr reactor, at a temperature, such as 100° C., to produce a4-amino-5-fluoro-6-chloro-picolinate of Formula (XI) (reaction g). The4-amino-5-fluoro-6-chloropicolinate of Formula (XI) can betransesterified to the corresponding methyl ester of Formula (XII) byreaction with titanium(IV) isopropoxide in methyl alcohol at refluxtemperature (reaction h).

As depicted in Scheme III, the 4-amino-5-fluoro-6-chloropicolinate ofFormula (XII) can be transformed into the3-iodo-4-amino-5-fluoro-6-chloropicolinate of Formula (XIII) viareaction with iodinating reagents, such as periodic acid and iodine, ina polar, protic solvent, such as methyl alcohol (reaction b₃). Stillecoupling of the 3-iodo-4-amino-5-fluoro-6-chloropicolinates of Formula(XIII) with a stannane, such as tributyl(vinyl)stannane, in the presenceof a catalyst, such as bis(triphenylphosphine)-palladium(II) dichloride,in a non-reactive solvent, such as 1,2-dichloroethane, at a temperature,such as 120-130° C., e.g., in a microwave reactor, provides3-(substituted)-4-amino-5-fluoro-6-chloropicolinates of Formula (XIV),wherein R² is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio(reaction c₃). Alternatively, the3-iodo-4-amino-5-fluoro-6-chloropicolinates of Formula (XIII) can betreated with cesium carbonate and a catalytic amount of both copper(I)iodide and 1,10-phenanthroline in the presence of a polar, proticsolvent, such as methyl alcohol, at a temperature, such as 65° C., toprovide a 3-(substituted)-4-amino-5-fluoro-6-chloropicolinic acids ofFormula (XIV), wherein R² is alkoxy or haloalkoxy (reaction i₁), whichcan be esterified to the methyl esters, e.g., by treatment with hydrogenchloride (gas) and methyl alcohol at 50° C. (reaction j₁). The3-(substituted)-4-amino-5-fluoro-6-chloropicolinates of Formula (XIV)can be converted to the 4-amino-6-substituted-picolinates of Formula(I-B), wherein Ar is as herein defined, via Suzuki coupling with aboronic acid or ester, in the presence of a base, such as potassiumfluoride, and a catalyst, such as bis(triphenylphosphine)-palladium(II)dichloride, in a polar, protic solvent mixture, such asacetonitrile-water, at a temperature, such as 110° C., e.g., in amicrowave reactor (reaction a₃).

Alternatively, the 4-amino-5-fluoro-6-chloropicolinates of Formula (XII)can be converted to the 4-amino-5-fluoro-6-substituted-picolinates ofFormula (XV), wherein Ar is as herein defined, via Suzuki coupling witha boronic acid or ester, in the presence of a base, such as potassiumfluoride, and a catalyst, such as bis(triphenylphosphine)-palladium(II)dichloride, in a polar, protic solvent mixture, such asacetonitrile-water, at a temperature, such as 110° C., e.g., in amicrowave reactor (reaction a₄). The4-amino-5-fluoro-6-substituted-picolinates of Formula (XV) can betransformed into the 3-iodo-4-amino-5-fluoro-6-substituted-picolinatesof Formula (XVI) via reaction with iodinating reagents, such as periodicacid and iodine, in a polar, protic solvent, such as methyl alcohol(reaction b₄). Stille coupling of the3-iodo-4-amino-5-fluoro-6-substituted-picolinates of Formula (XVI) witha stannane, such as tributyl(vinyl)stannane, in the presence of acatalyst, such as bis(triphenylphosphine)-palladium(II) dichloride, in anon-reactive solvent, such as 1,2-dichloroethane, at a temperature, suchas 120-130° C., e.g., in a microwave reactor, provides3-(substituted)-4-amino-5-fluoro-6-substituted-picolinates of Formula(I-B), wherein R² is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio(reaction c₄). Alternatively, the3-iodo-4-amino-5-fluoro-6-substituted-picolinates of Formula (XVI) canbe treated with cesium carbonate and a catalytic amount of bothcopper(I) iodide and 1,10-phenanthroline in the presence of a polar,protic solvent, such as methyl alcohol, at a temperature, such as 65°C., to provide a3-(substituted)-4-amino-5-fluoro-6-substituted-picolinic acids ofFormula (I-B), wherein R² is alkoxy or haloalkoxy (reaction i₂), whichcan be esterified to the methyl esters, e.g., by treatment with hydrogenchloride (gas) and methyl alcohol, at a temperature, such as 50° C.(reaction j₂).

As depicted in Scheme IV, the4-acetamido-6-(trimethylstannyl)picolinates of Formula (XVII) can beconverted to the 4-acetamido-6-substituted-picolinates of Formula(XVIII), wherein Ar is as herein defined, via Still coupling with anaryl bromide or aryl iodide, in the presence of a catalyst, such asbis(triphenylphosphine)-palladium(II) dichloride, in a solvent, such asdichloroethane, e.g., at reflux temperature (reaction k).4-Amino-6-substituted-picolinates of Formula (I-C), wherein Ar is asherein defined, can be synthesized from4-acetamido-6-substituted-picolinates of Formula (XVIII) via standarddeprotecting methods, such as hydrochloric acid gas in methanol(reaction l).

As depicted in Scheme V, 2,4-dichloro-5-methoxypyrimidine (XIX) can betransformed into 2,4-dichloro-5-methoxy-6-vinylpyrimidine (XX) via areaction with vinyl magnesium bromide, in a polar, aprotic solvent, suchas tetrahydrofuran (reaction m).2,4-Dichloro-5-methoxy-6-vinylpyrimidine (XX) can be transformed into2,6-dichloro-5-methoxypyrimidine-4-carboxaldehyde (XXI) via treatmentwith ozone, e.g., in a dichloromethane:methanol solvent mixture(reaction n). 2,6-Dichloro-5-methoxypyrimidine-4-carboxaldehyde (XXI)can be transformed into methyl2,6-dichloro-5-methoxypyrimidine-4-carboxylate (XXII) via treatment withbromine, e.g., in a methanol:water solvent mixture (reaction o). Methyl2,6-dichloro-5-methoxypyrimidine-4-carboxylate (XXII) can be transformedinto methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate (XXIII)via treatment with ammonia (e.g., 2 equivalents) in a solvent, such asDMSO (reaction p). Finally,6-amino-2-substituted-5-methoxypyrimidine-4-carboxylates of Formula(I-D), wherein Ar is as herein defined, can be prepared via Suzukicoupling with a boronic acid or ester, with6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate (XXIII), in thepresence of a base, such as potassium fluoride, and a catalyst, such asbis(triphenylphosphine)-palladium(II) dichloride, in a polar, proticsolvent mixture, such as acetonitrile-water, at a temperature, such as110° C., e.g., in a microwave reactor (reaction a₅).

The compounds of Formulae I-A, I-B, I-C, and I-D obtained by any ofthese processes, can be recovered by conventional means and purified bystandard procedures, such as by recrystallization or chromatography. Thecompounds of Formula (I) can be prepared from compounds of Formulae I-A,I-B, I-C, and I-D using standard methods well known in the art.

Compositions and Methods

In some embodiments, the compounds provided herein are employed inmixtures containing an herbicidally effective amount of the compoundalong with at least one agriculturally acceptable adjuvant or carrier.Exemplary adjuvants or carriers include those that are not phytotoxic orsignificantly phytotoxic to valuable crops, e.g., at the concentrationsemployed in applying the compositions for selective weed control in thepresence of crops, and/or do not react or significantly react chemicallywith the compounds of provided herein or other composition ingredients.Such mixtures can be designed for application directly to weeds or theirlocus or can be concentrates or formulations that are \diluted withadditional carriers and adjuvants before application. They can besolids, such as, for example, dusts, granules, water dispersiblegranules, or wettable powders, or liquids, such as, and for example,emulsifiable concentrates, solutions, emulsions or suspensions. They canalso be provided as a pre-mix or tank-mixed.

Suitable agricultural adjuvants and carriers that are useful inpreparing the herbicidal mixtures of the disclosure are well known tothose skilled in the art. Some of these adjuvants include, but are notlimited to, crop oil concentrate (mineral oil (85%)+emulsifiers (15%));nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammoniumsalt; blend of petroleum hydrocarbon, alkyl esters, organic acid, andanionic surfactant; C₉-C₁₁ alkylpolyglycoside; phosphated alcoholethoxylate; natural primary alcohol (C₁₂-C₁₆) ethoxylate;di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap;nonylphenol ethoxylate+urea ammonium nitrate; emulsified methylated seedoil; tridecyl alcohol (synthetic) ethoxylate (8 EO); tallow amineethoxylate (15 EO); PEG(400) dioleate-99.

Liquid carriers that can be employed include water and organic solvents.The organic solvents typically used include, but are not limited to,petroleum fractions or hydrocarbons such as mineral oil, aromaticsolvents, paraffinic oils, and the like; vegetable oils such as soybeanoil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconutoil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil,safflower oil, sesame oil, tung oil and the like; esters of the abovevegetable oils; esters of monoalcohols or dihydric, trihydric, or otherlower polyalcohols (4-6 hydroxy containing), such as 2-ethylhexylstearate, n-butyl oleate, isopropyl myristate, propylene glycoldioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate andthe like; esters of mono-, di- and poly-carboxylic acids and the like.Specific organic solvents include toluene, xylene, petroleum naphtha,crop oil, acetone, methyl ethyl ketone, cyclohexanone,trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butylacetate, propylene glycol monomethyl ether and diethylene glycolmonomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amylalcohol, ethylene glycol, propylene glycol, glycerine,N-methyl-2-pyrrolidinone, N,N-dimethyl alkylamides, dimethyl sulfoxide,liquid fertilizers, and the like. In some embodiments, water is thecarrier for the dilution of concentrates.

Suitable solid carriers include talc, pyrophyllite clay, silica,attapulgus clay, kaolin clay, kieselguhr, chalk, diatomaceous earth,lime, calcium carbonate, bentonite clay, Fuller's earth, cottonseedhulls, wheat flour, soybean flour, pumice, wood flour, walnut shellflour, lignin, and the like.

In some embodiments, one or more surface-active agents are utilized inthe compositions of the present disclosure. Such surface-active agentsare, in some embodiments, employed in both solid and liquidcompositions, e.g., those designed to be diluted with carrier beforeapplication. The surface-active agents can be anionic, cationic ornonionic in character and can be employed as emulsifying agents, wettingagents, suspending agents, or for other purposes. Surfactantsconventionally used in the art of formulation and which may also be usedin the present formulations are described, inter alia, in McCutcheon'sDetergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, N.J.,1998, and in Encyclopedia of Surfactants, Vol. I-III, ChemicalPublishing Co., New York, 1980-81. Typical surface-active agents includesalts of alkyl sulfates, such as diethanolammonium lauryl sulfate;alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate;alkylphenol-alkylene oxide addition products, such as nonylphenol-C₁₈ethoxylate; alcohol-alkylene oxide addition products, such as tridecylalcohol-C₁₆ ethoxylate; soaps, such as sodium stearate;alkylnaphthalene-sulfonate salts, such as sodiumdibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts,such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such assorbitol oleate; quaternary amines, such as lauryl trimethylammoniumchloride; polyethylene glycol esters of fatty acids, such aspolyethylene glycol stearate; block copolymers of ethylene oxide andpropylene oxide; salts of mono- and dialkyl phosphate esters; vegetableor seed oils such as soybean oil, rapeseed/canola oil, olive oil, castoroil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseedoil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and thelike; and esters of the above vegetable oils, e.g., methyl esters.

Oftentimes, some of these materials, such as vegetable or seed oils andtheir esters, can be used interchangeably as an agricultural adjuvant,as a liquid carrier or as a surface active agent.

Other adjuvants commonly used in agricultural compositions includecompatibilizing agents, antifoam agents, sequestering agents,neutralizing agents and buffers, corrosion inhibitors, dyes, odorants,spreading agents, penetration aids, sticking agents, dispersing agents,thickening agents, freezing point depressants, antimicrobial agents, andthe like. The compositions may also contain other compatible components,for example, other herbicides, plant growth regulants, fungicides,insecticides, and the like and can be formulated with liquid fertilizersor solid, particulate fertilizer carriers such as ammonium nitrate, ureaand the like.

The concentration of the active ingredients in the herbicidalcompositions of this disclosure is generally from about 0.001 to about98 percent by weight. Concentrations from about 0.01 to about 90 percentby weight are often employed. In compositions designed to be employed asconcentrates, the active ingredient is generally present in aconcentration from about 5 to about 98 weight percent, preferably about10 to about 90 weight percent. Such compositions are typically dilutedwith an inert carrier, such as water, before application. The dilutedcompositions usually applied to weeds or the locus of weeds generallycontain about 0.0001 to about 1 weight percent active ingredient andpreferably contain about 0.001 to about 0.05 weight percent.

The present compositions can be applied to weeds or their locus by theuse of conventional ground or aerial dusters, sprayers, and granuleapplicators, by addition to irrigation or flood water, and by otherconventional means known to those skilled in the art.

In some embodiments, the compounds and compositions described herein areapplied as a post-emergence application, pre-emergence application,in-water application to flooded paddy rice or water bodies (e.g., ponds,lakes and streams), or burn-down application.

In some embodiments, the compounds and compositions provided herein areutilized to control weeds in crops, including but not limited to citrus,apple, rubber, oil palm, forestry, direct-seeded, water-seeded andtransplanted rice, wheat, barley, oats, rye, sorghum, corn/maize,pastures, grasslands, rangelands, fallowland, turf, tree and vineorchards, aquatics, or row-crops, as well as non-crop settings, e.g.,industrial vegetation management or rights of way. In some embodiments,the compounds and compositions are used to control woody plants,broadleaf and grass weeds, or sedges.

In some embodiments, the compounds and compositions provided herein areutilized to control undesirable vegetation in rice. In certainembodiments, the undesirable vegetation is Brachiaria platyphylla(Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis(L.) Scop. (large crabgrass, DIGSA), Echinochloa crus-galli (L.) P.Beauv. (barnyardgrass, ECHCG), Echinochloa colonum (L.) LINK(junglerice, ECHCO), Echinochloa oryzoides (Ard.) Fritsch (earlywatergrass, ECHOR), Echinochloa oryzicola (Vasinger) Vasinger (latewatergrass, ECHPH), Ischaemum rugosum Salisb. (saramollagrass, ISCRU),Leptochloa chinensis (L.) Nees (Chinese sprangletop, LEFCH), Leptochloafascicularis (Lam.) Gray (bearded sprangletop, LEFFA), Leptochloapanicoides (Presl.) Hitchc. (Amazon sprangletop, LEFPA), Panicumdichotomiflorum (L.) Michx. (fall panicum, PANDI), Paspalum dilatatumPoir. (dallisgrass, PASDI), Cyperus difformis L. (smallflower flatsedge,CYPDI), Cyperus esculentus L. (yellow nutsedge, CYPES), Cyperus iria L.(rice flatsedge, CYPIR), Cyperus rotundus L. (purple nutsedge, CYPRO),Eleocharis species (ELOSS), Fimbristylis miliacea (L.) Vahl (globefringerush, FIMMI), Schoenoplectus juncoides Roxb. (Japanese bulrush,SPCJU), Schoenoplectus maritimus L. (sea clubrush, SCPMA),Schoenoplectus mucronatus L. (ricefield bulrush, SCPMU), Aeschynomenespecies, (jointvetch, AESSS), Alternanthera philoxeroides (Mart.)Griseb. (alligatorweed, ALRPH), Alisma plantago-aquatica L. (commonwaterplantain, ALSPA), Amaranthus species, (pigweeds and amaranths,AMASS), Ammannia coccinea Rottb. (redstem, AMMCO), Eclipta alba (L.)Hassk. (American false daisy, ECLAL), Heteranthera limosa (SW.)Willd./Vahl (ducksalad, HETLI), Heteranthera reniformis R. & P.(roundleaf mudplantain, HETRE), Ipomoea hederacea (L.) Jacq. (ivyleafmorningglory, IPOHE), Lindernia dubia (L.) Pennell (low false pimpernel,LIDDU), Monochoria korsakowii Regel & Maack (monochoria, MOOKA),Monochoria vaginalis (Burm. F.) C. Presl ex Kuhth, (monochoria, MOOVA),Murdannia nudiflora (L.) Brenan (doveweed, MUDNU), Polygonumpensylvanicum L., (Pennsylvania smartweed, POLPY), Polygonum persicariaL. (ladysthumb, POLPE), Polygonum hydropiperoides Michx. (POLHP, mildsmartweed), Rotala indica (Willd.) Koehne (Indian toothcup, ROTIN),Sagittaria species, (arrowhead, SAGSS), Sesbania exaltata (Raf.)Cory/Rydb. Ex Hill (hemp sesbania, SEBEX), or Sphenoclea zeylanicaGaertn. (gooseweed, SPDZE).

In some embodiments, the compounds and compositions provided herein areutilized to control undesirable vegetation in cereals. In certainembodiments, the undesirable vegetation is Alopecurus myosuroides Huds.(blackgrass, ALOMY), Apera spica-venti (L.) Beauv. (windgrass, APESV),Avena fatua L. (wild oat, AVEFA), Bromus tectorum L. (downy brome,BROTE), Lolium multiflorum Lam. (Italian ryegrass, LOLMU), Phalarisminor Retz. (littleseed canarygrass, PHAMI), Poa annua L. (annualbluegrass, POANN), Setaria pumila (Poir.) Roemer & J. A. Schultes(yellow foxtail, SETLU), Setaria viridis (L.) Beauv. (green foxtail,SETVI), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Galiumaparine L. (catchweed bedstraw, GALAP), Kochia scoparia (L.) Schrad.(kochia, KCHSC), Lamium purpureum L. (purple deadnettle, LAMPU),Matricaria recutita L. (wild chamomile, MATCH), Matricariamatricarioides (Less.) Porter (pineappleweed, MATMT), Papaver rhoeas L.(common poppy, PAPRH), Polygonum convolvulus L. (wild buckwheat, POLCO),Salsola tragus L. (Russian thistle, SASKR), Stellaria media (L.) Vill.(common chickweed, STEME), Veronica persica Poir. (Persian speedwell,VERPE), Viola arvensis Murr. (field violet, VIOAR), or Viola tricolor L.(wild violet, VIOTR).

In some embodiments, the compounds and compostions provided herein areutilized to control undesirable vegetation in range and pasture. Incertain embodiments, the undesirable vegetation is Ambrosiaartemisiifolia L. (common ragweed, AMBEL), Cassia obtusifolia (sicklepod, CASOB), Centaurea maculosa auct. non Lam. (spotted knapweed,CENMA), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Convolvulusarvensis L. (field bindweed, CONAR), Euphorbia esula L. (leafy spurge,EPHES), Lactuca serriola L./Torn. (prickly lettuce, LACSE), Plantagolanceolata L. (buckhorn plantain, PLALA), Rumex obtusifolius L.(broadleaf dock, RUMOB), Sida spinosa L. (prickly sida, SIDSP), Sinapisarvensis L. (wild mustard, SINAR), Sonchus arvensis L. (perennialsowthistle, SONAR), Solidago species (goldenrod, SOOSS), Taraxacumofficinale G. H. Weber ex Wiggers (dandelion, TAROF), Trifolium repensL. (white clover, TRFRE), or Urtica dioica L. (common nettle, URTDI).

In some embodiments, the compounds and compositions provided herein areutilized to control undesirable vegetation found in row crops. Incertain embodiments, the undesirable vegetation is Alopecurusmyosuroides Huds. (blackgrass, ALOMY), Avena fatua L. (wild oat, AVEFA),Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP),Digitaria sanguinalis (L.) Scop. (large crabgrass, DIGSA), Echinochloacrus-galli (L.) P. Beauv. (barnyardgrass, ECHCG), Echinochloa colonum(L.) Link (junglerice, ECHCO), Lolium multiflorum Lam. (Italianryegrass, LOLMU), Panicum dichotomiflorum Michx. (fall panicum, PANDI),Panicum miliaceum L. (wild-proso millet, PANMI), Setaria faberi Herrm.(giant foxtail, SETFA), Setaria viridis (L.) Beauv. (green foxtail,SETVI), Sorghum halepense (L.) Pers. (Johnsongrass, SORHA), Sorghumbicolor (L.) Moench ssp. Arundinaceum (shattercane, SORVU), Cyperusesculentus L. (yellow nutsedge, CYPES), Cyperus rotundus L. (purplenutsedge, CYPRO), Abutilon theophrasti Medik. (velvetleaf, ABUTH),Amaranthus species (pigweeds and amaranths, AMASS), Ambrosiaartemisiifolia L. (common ragweed, AMBEL), Ambrosia psilostachya DC.(western ragweed, AMBPS), Ambrosia trifida L. (giant ragweed, AMBTR),Asclepias syriaca L. (common milkweed, ASCSY), Chenopodium album L.(common lambsquarters, CHEAL), Cirsium arvense (L.) Scop. (Canadathistle, CIRAR), Commelina benghalensis L. (tropical spiderwort, COMBE),Datura stramonium L. (jimsonweed, DATST), Daucus carota L. (wild carrot,DAUCA), Euphorbia heterophylla L. (wild poinsettia, EPHHL), Erigeronbonariensis L. (hairy fleabane, ERIBO), Erigeron canadensis L. (Canadianfleabane, ERICA), Helianthus annuus L. (common sunflower, HELAN),Jacquemontia tamnifolia (L.) Griseb. (smallflower morningglory, IAQTA),Ipomoea hederacea (L.) Jacq. (ivyleaf morningglory, IPOHE), Ipomoealacunosa L. (white morningglory, IPOLA), Lactuca serriola L./Torn.(prickly lettuce, LACSE), Portulaca oleracea L. (common purslane,POROL), Sida spinosa L. (prickly sida, SIDSP), Sinapis arvensis L. (wildmustard, SINAR), Solanum ptychanthum Dunal (eastern black nightshade,SOLPT), or Xanthium strumarium L. (common cocklebur, XANST).

In some embodiments, application rates of about 1 to about 4,000grams/hectare (g/ha) are employed in post-emergence operations. In someembodiments, rates of about 1 to about 4,000 g/ha are employed inpre-emergence operations.

In some embodiments, the compounds, compositions, and methods providedherein are used in conjunction with one or more other herbicides tocontrol a wider variety of undesirable vegetation When used inconjunction with other herbicides, the presently claimed compounds canbe formulated with the other herbicide or herbicides, tank-mixed withthe other herbicide or herbicides or applied sequentially with the otherherbicide or herbicides. Some of the herbicides that can be employed inconjunction with the compounds of the present disclosure include: 4-CPA;4-CPB; 4-CPP; 2,4-D; 2,4-D choline salt, 2,4-D esters and amines;2,4-DB; 3,4-DA; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T;2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor,allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn,amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor,aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos,anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron,aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone,benfluralin, benfuresate, bensulfuron-methyl, bensulide, benthiocarb,bentazon-sodium, benzadox, benzfendizone, benzipram, benzobicyclon,benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone,bifenox, bilanafos, bispyribac-sodium, borax, bromacil, bromobonil,bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor,butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin,butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calciumchlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide,carboxazole chlorprocarb, carfentrazone-ethyl, CDEA, CEPC,chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine,chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop,chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen,chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham,chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin,cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop-propargyl,clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid,cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol,cumyluron, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim,cycluron, cyhalofop-butyl, cyperquat, cyprazine, cyprazole, cypromid,daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn,di-allate, dicamba, dichlobenil, dichloralurea, dichlormate,dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat,diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican,diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn,dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine,dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid,dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP,eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin,ethbenzamide, ethametsulfuron, ethidimuron, ethiolate, ethobenzamid,etobenzamid, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen,etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop,fenoxaprop-P-ethyl, fenoxaprop-P-ethyl+isoxadifen-ethyl, fenoxasulfone,fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate,flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop,fluazifop-P-butyl, fluazolate, flucarbazone, flucetosulfuron,fluchloralin, flufenacet, flufenican, flufenpyr-ethyl, flumetsulam,flumezin, flumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron,fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron,flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone,flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen,foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-ammonium,glyphosate, halosafen, halosulfuron-methyl, haloxydine,haloxyfop-methyl, haloxyfop-P-methyl, halauxifen-methyl,hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox,imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan,indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron,ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil,isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon,isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop,karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA,esters and amines, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P,medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron,mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron,metflurazon, methabenzthiazuron, methalpropalin, methazole,methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methylbromide, methyl isothiocyanate, methyldymron, metobenzuron,metobromuron, metolachlor, metosulam, metoxuron, metribuzin,metsulfuron, molinate, monalide, monisouron, monochloroacetic acid,monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide,naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen,nitrofluorfen, norflurazon, noruron, OCH, orbencarb,ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon,oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paraflufen-ethyl,parafluron, paraquat, pebulate, pelargonic acid, pendimethalin,penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone,pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl,phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden,piperophos, potassium arsenite, potassium azide, potassium cyanate,pretilachlor, primisulfuron-methyl, procyazine, prodiamine, profluazol,profluralin, profoxydim, proglinazine, prohexadione-calcium, prometon,prometryn, propachlor, propanil, propaquizafop, propazine, propham,propisochlor, propoxycarbazone, propyrisulfuron, propyzamide,prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon,pyraclonil, pyraflufen, pyrasulfotole, pyrazogyl, pyrazolynate,pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor,pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan,pyrithiobac-methyl, pyroxasulfone, pyroxsulam, quinclorac, quinmerac,quinoclamine, quinonamid, quizalofop, quizalofop-P-ethyl, rhodethanil,rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton,sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite,sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone,sulfometuron, sulfosate, sulfosulfuron, sulfuric acid, sulglycapin,swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione,tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton,terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron,thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl,thifensulfuron, thiobencarb, tiocarbazil, tioclorim, topramezone,tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam,tribenuron, tricamba, triclopyr esters and amines, tridiphane,trietazine, trifloxysulfuron, trifluralin, triflusulfuron, trifop,trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac,tritosulfuron, vernolate and xylachlor.

The compounds and compositions of the present disclosure can generallybe employed in combination with known herbicide safeners, such asbenoxacor, benthiocarb, brassinolide, cloquintocet (e.g., mexyl),cyometrinil, daimuron, dichlormid, dicyclonon, dimepiperate, disulfoton,fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole,harpin proteins, isoxadifen-ethyl, mefenpyr-diethyl, MG 191, MON 4660,naphthalic anhydride (NA), oxabetrinil, R29148 andN-phenylsulfonylbenzoic acid amides, to enhance their selectivity.

The compounds, compositions, and methods described herein be used tocontrol undesirable vegetation on glyphosate-tolerant-,glufosinate-tolerant-, dicamba-tolerant-, phenoxy auxin-tolerant-,pyridyloxy auxin-tolerant-, aryloxyphenoxypropionate-tolerant-, acetylCoA carboxylase (ACCase) inhibitor-tolerant-, imidazolinone-tolerant-,acetolactate synthase (ALS) inhibitor-tolerant-,4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitor -tolerant-,protoporphyrinogen oxidase (PPO) inhibitor -tolerant-,triazine-tolerant-, bromoxynil-tolerant-crops (such as, but not limitedto, soybean, cotton, canola/oilseed rape, rice, cereals, corn, turf,etc), for example, in conjunction with glyphosate, glufosinate, dicamba,phenoxy auxins, pyridyloxy auxins, aryloxyphenoxypropionates, ACCaseinhibitors, imidazolinones, ALS inhibitors, HPPD inhibitors, PPOinhibitors, triazines, and bromoxynil The compositions and methods maybe used in controlling undesirable vegetation in crops possessingmultiple or stacked traits conferring tolerance to multiple chemistriesand/or inhibitors of multiple modes of action.

The compounds and compositions provided herein may also be employed tocontrol herbicide resistant or tolerant weeds. Exemplary resistant ortolerant weeds include, but are not limited to, biotypes resistant ortolerant to acetolactate synthase (ALS) inhibitors, photosystem IIinhibitors, acetyl CoA carboxylase (ACCase) inhibitors, syntheticauxins, photosystem I inhibitors, 5-enolpyruvylshikimate-3-phosphate(EPSP) synthase inhibitors, microtubule assembly inhibitors, lipidsynthesis inhibitors, protoporphyrinogen oxidase (PPO) inhibitors,carotenoid biosynthesis inhibitors, very long chain fatty acid (VLCFA)inhibitors, phytoene desaturase (PDS) inhibitors, glutamine synthetaseinhibitors, 4-hydroxyphenyl-pyruvate-dioxygenase (HPPD) inhibitors,mitosis inhibitors, cellulose biosynthesis inhibitors, herbicides withmultiple modes-of-action such as quinclorac, and unclassified herbicidessuch as arylaminopropionic acids, difenzoquat, endothall, andorganoarsenicals. Exemplary resistant or tolerant weeds include, but arenot limited to, biotypes with resistance or tolerance to multipleherbicides, multiple chemical classes, and multiple herbicidemodes-of-action.

The described embodiments and following examples are for illustrativepurposes and are not intended to limit the scope of the claims. Othermodifications, uses, or combinations with respect to the compositionsdescribed herein will be apparent to a person of ordinary skill in theart without departing from the spirit and scope of the claimed subjectmatter.

Synthesis of Precursers Preparation 1: Methyl4-amino-3,6-dichloropicolinate (Head A)

Prepared as described in Fields et al., WO 2001051468 A1.

Preparation 2: Methyl 4-amino-3,6-dichloro-5-fluoropicolinate (Head B)

Prepared as described in Fields et al., Tetrahedron Letters (2010),51(1), 79-81.

Preparation 3: 2,6-Dichloro-5-methoxy-4-vinyl pyrimidine

To a solution of commercially available 2,6-dichloro-5-methoxypyrimidine (100 g, 0.55 mol) in dry tetrahydrofuran was added, dropwise,1M vinyl magnesium bromide in tetrahydrofuran solvent (124 g, 0.94 mol)over one hour (h) at room temperature. The mixture was then stirred for4 h at room temperature. Excess Grignard reagent was quenched byaddition of acetone (200 mL) while the temperature of the mixture wasmaintained at a temperature below 20° C. Thereafter,2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) (151 g, 0.67 mol) wasadded at once and stirred overnight. A yellow solid precipitated out.The solid was filtered and washed with ethyl acetate (500 mL). Thefiltrate was concentrated under reduced pressure and the resulting crudecompound was diluted with ethyl acetate (2 L). The resultingundissolved, dark, semi-solid was separated by filtration using ethylacetate. It was further concentrated under reduced pressure to provide acrude compound, which was purified by column chromatography. Thecompound was eluted with 5% to 10% ethyl acetate in hexane mixture toprovide the title compound (70 g, 60%): mp 60-61° C.; ¹H NMR (CDCl₃) δ3.99 (s, 3H), 5.85 (d, 1H), 6.75 (d, 1H), 6.95 (dd, 1H).

Preparation 4: 2,6-Dichloro-5-methoxy-pyrimidine-4-carbaldehyde

A solution of 2,6-dichloro-5-methoxy-4-vinyl pyrimidine (50 g, 0.24 mol)in dichloromethane:methanol (4:1, 2L) was cooled to −78° C. Ozone gaswas bubbled therethrough for 5 h. The reaction was quenched withdimethyl sulfide (50 mL). The mixture was slowly warmed to roomtemperature and concentrated under reduced pressure at 40° C. to providethe title compound (50.5 g, 100%); HPLC (85% acetonitrile buffered with0.1% v/v acetic acid).

Preparation 5: Methyl 2,6-dichloro-5-methoxy-pyrimidine-4-carboxylate

A solution of 2,6-dichloro-5-methoxy-pyrimidine-4-carbaldehyde (50 g,0.24 mol) in methanol (1 L) and water (60 mL) was prepared. To thesolution, sodium bicarbonate (400 g) was added. A 2 M solution ofbromine (192 g, 1.2 mol) in methanol/water (600 mL, 9:1 was added,dropwise, to the pyrimidine solution for 45 minutes (min) at 0° C. whilestirring the mixture. The stirring was continued at the same temperaturefor 1 h. Later, the mixture was stirred at room temperature for 4 h.While stirring, the reaction mixture was thereafter poured onto amixture of crushed ice (2 L), sodium bisulfite (50 g), and sodiumchloride (200 g). The product was extracted with ethyl acetate (1L×2),and the combined organic layer was dried over sodium sulfate andfiltered. Evaporation of the solvent under reduced pressure produced athick material, which solidified on long standing to afford the titlecompound (50.8 g, 87%); ESIMS m/z 238 ([M+H]⁺).

Preparation 6: Methyl6-amino-2-chloro-5-methoxy-pyrimidine-4-carboxylate (Head C)

A solution of methyl 2,6-dichloro-5-methoxy-pyrimidine-4-carboxylate (25g, 0.1 mol) and dimethyl sulfoxide (DMSO) was prepared. To this solutionwas added, at 0-5° C., a solution of ammonia (2 eq) in DMSO. Thismixture was stirred at the same 0-5° C. temperature for 10 to 15 min.Later, the mixture was diluted with ethyl acetate, and the resultingsolid was filtered off. The ethyl acetate filtrate was washed with abrine solution and dried over sodium sulfate. Upon concentration, thecrude product was obtained. The crude product was stirred in a minimumamount of ethyl acetate and filtered to obtain the pure compound.Additional pure compound was obtained from the filtrate which, afterconcentration, was purified by flash chromatography. This produced thetitle compound (11 g, 50%): mp 158° C.; ¹H NMR (DMSO-d₆) δ 3.71 (s, 3H),3.86 (s, 3H), 7.65 (brs, 1H), 8.01 (brs, 1H).

Preparation 7: Methyl 4-amino-3,6-dichloro-5-iodopicolinate

Methyl 4-amino-3,6-dichloropicolinate (10.0 g, 45.2 mmol), periodic acid(3.93 g, 17.2 mmol), and iodine (11.44 g, 45.1 mmol) were dissolved inmethanol (30 mL) and refluxed at 60° C. for 27 h. The reaction mixturewas concentrated, diluted with diethyl ether, and washed twice withsaturated aqueous sodium bisulfite. The aqueous layers were extractedonce with diethyl ether, and the combined organic layers were dried overanhydrous sodium sulfate. The product was concentrated and purified byflash chromatography (silica gel, 0-50% ethyl acetate/hexanes) toprovide the title compound as a pale yellow solid (12.44 g, 35.9 mmol,79%): mp 130.0-131.5° C.; ¹H NMR (400 MHz, CDCl₃) δ 5.56 (s, 2H), 3.97(s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 163.80, 153.00, 152.75, 145.63,112.12, 83.91, 53.21; EIMS m/z 346.

Preparation 8: Methyl 4-amino-3,6-dichloro-5-methylpicolinate (Head D)

A mixture of methyl 4-amino-3,6-dichloro-5-iodopicolinate (8.1 g, 23.4mmol), tetramethylstannane (8.35 g, 46.7 mmol), andbis(triphenylphosphine)palladium(II) chloride (2.5 g, 3.5 mmol) in1,2-dichloroethane (40 mL) was irradiated in a Biotage Initiatormicrowave at 120° C. for 30 min, with external IR-sensor temperaturemonitoring from the side. The reaction mixture was loaded directly ontoa silica gel cartridge and purified by flash chromatography (silica gel,0-50% ethyl acetate/hexanes) to provide the title compund as an orangesolid (4.53 g, 19.27 mmol, 83%): mp 133-136° C.; ¹H NMR (400 MHz, CDCl₃)δ 4.92 (s, 2H), 3.96 (s, 3H), 2.29 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ164.34, 150.24, 148.69, 143.94, 117.01, 114.60, 53.02, 14.40; ESIMS m/z236 ([M+H]⁺), 234 ([M+H]⁻).

Preparation 9: Methyl 6-amino-2,5-dichloropyrimidine-4-carboxylate (HeadE)

Prepared as described in Epp et al., WO 2007082076 A1.

Preparation 10: Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate(Head F)

Prepared as described in Epp et al., WO 2013003740 A1.

Preparation 11: Methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate (HeadG)

Methyl 4-amino-6-chloro-5-fluoro-3-iodopicolinate (7.05 g, 21.33 mmol,prepared as described in Epp et al., WO 2013003740 A1) andvinyltri-n-butyltin (7.52 mL, 25.6 mmol) were suspended indichloroethane (71.1 mL) and the mixture was degassed with Argon for 10min bis(triphenylphosphine)palladium(II) chloride (1.497 g, 2.133 mmol)was then added and the reaction mixture was stirred at 70° C. overnight(clear orange solution). The reaction was monitored by GCMS. After 20 h,the reaction mixture was concentrated, adsorbed onto Celite, andpurified by column chromatography (SiO2, hexanes/ethyl acetate gradient)to afford the title compound as a light brown solid (3.23 g, 65.7%) as alight brown solid: mp 99-100° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.87 (dd,J=18.1, 11.6 Hz, 1H), 5.72 (dd, J=11.5, 1.3 Hz, 1H), 5.52 (dd, J=18.2,1.3 Hz, 1H), 4.79 (s, 2H), 3.91 (s, 3H); ¹⁹F NMR (376 MHz, CDCl₃)δ-138.79 (s); EIMS m/z 230.

Preparation 12: Methyl 4-amino-3,5,6-trichloropicolinate (Head H)

Prepared as described in Finkelstein et al., WO 2006062979 A1.

Preparation 13: Methyl 4-amino-6-bromo-3-chloro-5-fluoropicolinate (HeadI)

Prepared as described in Arndt et al., US 20120190857 A1.

Preparation 14: Methyl4-amino-3-chloro-5-fluoro-6-(trimethylstannyl)picolinate (Head J)

Methyl 4-amino-6-bromo-3-chloro-5-fluoropicolinate (500 mg, 1.8 mmol),1,1,1,2,2,2-hexamethyldistannane (580 mg, 1.8 mmol) andbis(triphenylphosphine)-palladium(II) chloride (120 mg, 0.18 mmol) werecombined in 6 mL dry dioxane, sparged with a stream of nitrogen for 10min and then heated to 80° C. for 2 h. The cooled mixture was stirredwith 25 mL ethyl acetate and 25 mL saturated NaCl for 15 min. Theorganic phase was separated, filtered through diatomaceous earth, dried(Na₂SO₄) and evaporated. The residue was taken up in 4 mL ethyl acetate,stirred and treated in portions with 15 mL hexane. The milky whitesolution was decanted from any solids produced, filtered through glasswool and evaporated to give the title compound as an off-white solid(660 mg, 100%): ¹H NMR (400 MHz, CDCl₃) δ 4.63 (d, J=29.1 Hz, 1H), 3.97(s, 2H), 0.39 (s, 4H); ¹⁹F NMR (376 MHz, CDCl₃) δ −130.28; EIMS m/z 366.

Preparation 15: Methyl4-acetamido-3-chloro-6-(trimethylstannyl)-picolinate (Head K)

Prepared as described in Balko et al., WO 2003011853 A1.

Preparation 16: Methyl 4-acetamido-3,6-dichloropicolinate (Head L)

Prepared as described in Fields et al., WO 2001051468 A1.

Preparation 17: Methyl 4-amino-3-chloro-6-iodopicolinate (Head M)

Prepared as described in Balko et al., WO 2007082098 A2.

Preparation 18: Methyl 4-acetamido-3-chloro-6-iodopicolinate (Head N)

Prepared as described in Balko et al., WO 2007082098 A2.

Preparation 19: Methyl 4-amino-6-bromo-3,5-difluoropicolinate (Head O)

Prepared as described in Fields et al., WO 2001051468 A1.

Preparation 20: Methyl 6-amino-2-chloro-5-vinylpyrimidine-4-carboxylate(Head P)

Prepared as described in Epp et al., US20090088322.

Preparation 21: 1-Bromo-4-(2,2-diethoxyethoxy)-2-fluorobenzene

4-Bromo-3-fluorophenol (7 g, 0.03665 mol) and potassium carbonate (7.6g, 0.055 mol) were dissolved in N,N-dimethylformamide (9 mL).2-Bromo-1,1-diethoxyethane (8.5 mL, 0.055 mol) was added and thereaction mixture was stirred and heated to 135° C. for 7 h. The solventwas removed after the reaction was completed. The residue was dissolvedin ethyl acetate and washed with 2M NaOH solution. The organic phase wasdried over Na₂SO₄. The solvent was evaporated to yield1-bromo-4-(2,2-diethoxyethoxy)-2-fluorobenzene as an oil (11.4 g, 100%).

Preparation 22: 1-Bromo-3-(2,2-diethoxyethoxy)-2-fluorobenzene

1-bromo-3-(2,2-diethoxyethoxy)-2-fluorobenzene was prepared from3-bromo-2-fluorophenol as described in Preparation 81.

Preparation 23: 2-Bromo-4-(2,2-diethoxyethoxy)-1-fluorobenzene

2-bromo-4-(2,2-diethoxyethoxy)-1-fluorobenzene was prepared from3-bromo-4-fluorophenol as described in Preparation 81.

Preparation 24: 1-Bromo-4-chloro-2-(2,2-diethoxyethoxy)benzene

1-bromo-4-chloro-2-(2,2-diethoxyethoxy)benzene was prepared from2-bromo-5-chlorophenol as described in Preparation 81.

Preparation 25: (4-Bromo-3-fluorophenyl)(2,2-diethoxyethyl)sulfane

(4-bromo-3-fluorophenyl)(2,2-diethoxyethyl)sulfane was prepared from4-bromo-3-fluorobenzenethiol as described in Preparation 81.

Preparation 26: 4-Bromo-7-chlorobenzofuran

To 80 mL of benzene was added polyphosphoric acid (3.47 g, 36.9 mmol)and commercially available 2-(5-bromo-2-chlorophenoxy)acetaldehyde (9.2g, 36.9 mmol) and separated into eight 20 mL vials containing equalamounts. The vials were heated with an external temperature of 90° C.for 4 days. Upon cooling of the reaction, the benzene was removed bydecanting. Celite (50 g) was added to the organic solution and thesolvent was removed using a rotary evaporator. The impregnated Celitewas loaded onto a Teledyne-Isco purification system and purified bysilica gel chromatography using 0-30% ethyl acetate:hexanes to give4-bromo-7-chlorobenzofuran as a white solid (2.7 g, 32%): ¹H NMR (400MHz, CDCl₃) δ 7.73 (d, J=2.2 Hz, 1H), 7.33 (d, J=8.3 Hz, 1H), 7.18 (d,J=8.3 Hz, 1H), 6.85 (d, J=2.2 Hz, 1H);¹³C NMR (101 MHz, CDCl₃) δ 150.38(s), 146.14 (s), 130.27 (s), 126.56 (s), 125.32 (s), 116.44 (s), 112.49(s), 107.71 (s); ESIMS m/z 232 ([M+H]⁺), 230 ([M−H]⁻).

Preparation 27: 6-Bromobenzofuran and 4-bromobenzofuran

6-Bromobenzofuran and 4-bromobenzofuran were prepared as described inUS20040147559 from 1-bromo-3-(2,2-diethoxyethoxy)benzene.

Preparation 28: 5-Bromo-6-fluorobenzofuran and5-bromo-4-fluorobenzofuran

1-Bromo-4-(2,2-diethoxyethoxy)-2-fluorobenzene (11.4 g, 0.037 mol) wasdissolved in toluene (78 mL). Polyphosphoric acid (11.9 g) was added andthe mixture was heated to reflux for 5 h. The solvent was removed andthe residue was diluted with water and ethyl acetate. The organic phasewas washed with 2M NaOH solution and then dried over Na₂SO₄. A mixtureof 5-bromo-6-fluorobenzofuran and 5-bromo-4-fluorobenzofuran (4.8 g,60.3%) were obtained as a mixture after purification via columnchromatography.

Preparation 29: 6-Bromo-7-fluorobenzofuran

6-Bromo-7-fluorobenzofuran was prepared from1-bromo-3-(2,2-diethoxyethoxy)-2-fluorobenzene as described inPreparation 88; ESIMS m/z 216 ([M+H]⁺).

Preparation 30: 6-Bromo-5-fluorobenzofuran

6-Bromo-5-fluorobenzofuran was prepared from2-bromo-4-(2,2-diethoxyethoxy)-1-fluorobenzene as described inPreparation 88: ESIMS m/z 216 ([M+H]⁺).

Preparation 31: 7-Bromo-4-chlorobenzofuran

7-Bromo-4-chlorobenzofuran was prepared from1-bromo-4-chloro-2-(2,2-diethoxyethoxy)benzene as described inPreparation 88; ESIMS m/z 232 ([M+H]⁺).

Preparation 32: 5-Bromo-4-fluorobenzo[b]thiophene and5-bromo-6-fluorobenzo[b]thiophene

Polyphosphoric acid (13.9 g) was stirred in chlorobenzene (50 mL) at130° C. (4-bromo-3-fluorophenyl)(2,2-diethoxyethyl)sulfane (7.7 g,0.0238 mol) in chlorobenzene (15.4 mL) was added dropwise at 130° C. Themixture was then stirred at 130° C. for 10 h. The solvent was removedand the residue was extracted with toluene, hexane, and then water. Theorganic phase was combined and washed with saturated NaHCO₃ solution andbrine, and then dried over Na₂SO₄. The products5-bromo-4-fluorobenzo[b]thiophene and 5-bromo-6-fluorobenzo[b]thiophenewere obtained after purification via column chromatography (3.6 g,65.5%).

Preparation 33: Bromo-5-fluorobenzo[b]thiophene and4-bromo-5-fluorobenzo[b]thiophene

6-Bromo-5-fluorobenzo[b] thiophene and 4-bromo-5-fluorobenzo[b]thiophene were prepared from(3-bromo-4-fluorophenyl)(2,2-diethoxyethyl)sulfane as described inPreparation 81: ESIMS m/z 232 ([M+H]⁺).

Preparation 34:2-(7-Chlorobenzofuran-4-yl)-5,5-dimethyl-1,3,2-dioxaborinane

2-(7-Chlorobenzofuran-4-yl)-5,5-dimethyl-1,3,2-dioxaborinane wasprepared as described in Preparation 94 from 4-bromo-7-chlorobenzofuran(prepared as described in WO2005056015) to afford a white solid (66%):IR (cm⁻¹) 669.18,701.26, 741.33, 792.08, 773.25, 842.53, 811.66, 863.44,876.27, 884.51, 953.31, 993.58, 1027.34, 1132.28, 1059.34, 1157.92,1217.21, 1207.86, 1253.95, 1238.65, 1302.38, 1266.72, 1359.16, 1335.94,1370.05, 1422.73, 1438.38, 1480.37, 1577.30, 1602.05, 2903.59, 2871.91,2940.30, 2955.31, 3140.15, 3161.21; ¹H NMR (400 MHz, CDCl₃) δ 7.69 (d,J=2.1 Hz, 1H), 7.63 (d, J=7.8 Hz, 1H), 7.28 (dd, J=6.7, 2.6 Hz, 1H),7.27 (d, J=2.2 Hz, 1H), 3.82 (s, 4H), 1.05 (s, 6H); ESIMS m/z 265([M+H]⁺), 263 ([M−H]⁻).

Preparation 35:2-(Benzofuran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and2-(benzofuran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

2-(Benzofuran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and2-(benzofuran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wereprepared as described in Preparation 94 from 4-bromobenzofuran and6-bromobenzofuran to afford the mixture as a clear oil (48%): ¹H NMR(400 MHz, CDCl₃) δ 7.97 (s, 1H), 7.72-7.68 (m, 1H), 7.66 (dd, J=4.9, 2.6Hz, 2H), 7.60 (dd, J=8.0, 5.2 Hz, 2H), 7.30 (dd, J=7.1, 6.2 Hz, 1H),7.28-7.21 (m, 2H), 6.77 (dd, J=2.1, 0.8 Hz, 1H), 1.37 (d, J=6.2 Hz,22H), 1.29-1.22 (m, 8H); ¹³C NMR (101 MHz, CDCl₃) δ 146.01, 145.21,130.19, 130.11, 128.76, 123.56, 120.60, 117.60, 114.05, 108.45, 106.63,83.82, 83.69, 83.50, 25.02, 24.98, 24.88; ESIMS m/z 245 ([M+H]⁺), 243([M−H]⁻).

Preparation 36:2-(6-Fluorobenzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and2-(4-fluorobenzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

A mixture of 5-bromo-6-fluorobenzofuran and 5-bromo-4-fluorobenzofuran(1 combined equivalent), KOAc (3 eq) and bis(pinacolato) diboron (1.2eq) were stirred in dioxane (0.1M with respect to5-bromo-6-fluorobenzofuran and 5-bromo-4-fluorobenzofuran mixture) undernitrogen flow for 30 min. The catalyst PdCl₂(dppf) 0.15 eq) was addedand the nitrogen flow was maintained for 10 min. The reaction mixturewas heated to 85° C. overnight. The solvent was removed, the residue wasdissolved in methylene dichloride, and the solid was filtered. Thefiltrate was concentrated and purified through a column to give amixture of2-(6-fluorobenzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and2-(4-fluorobenzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(63%): ¹H NMR (400 MHz, CDCl₃) δ 7.98 (d, J=5.7 Hz, 1H), 7.59 (d, J=2.1Hz, 1H), 7.18 (d, J=9.4 Hz, 1H), 6.73 (d, J=1.3 Hz, 1H), 1.38 (s, 12H);¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J=7.0 Hz, 1H), 7.37 (t, J=7.4 Hz,1H), 7.30 (d, J=8.4 Hz, 1H), 6.87 (s, 1H), 1.38 (s, 12H); ¹⁹F NMR (376MHz, CDCl₃) δ −107.80, −107.81, −107.82, −107.84, −108.47, −108.48;ESIMS m/z 262 ([M+H]⁺).

Preparation 37:2-(4-Chlorobenzofuran-7-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

2-(4-Chlorobenzofuran-7-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasprepared as described in Preparation 98 from 7-bromo-4-chlorobenzofuran:¹H NMR (400 MHz, CDCl₃) δ 7.75 (d, J=2.2 Hz, 1H), 7.67 (d, J=7.8 Hz,1H), 7.24 (d, J=7.8 Hz, 1H), 6.86 (d, J=2.2 Hz, 1H), 1.41 (s, 12H);ESIMS m/z 278 ([M+H]⁺).

Preparation 38:2-(5-Fluorobenzofuran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

2-(5-Fluorobenzofuran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasprepared as described in Preparation 98 from 6-bromo-5-fluorobenzofuran:¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=4.3 Hz, 1H), 7.68 (d, J=2.2 Hz,1H), 7.24-7.20 (m, 1H), 6.75-6.70 (m, 1H), 1.38 (s, 12H);¹⁹F NMR (376MHz, CDCl₃) δ −110.23 (dd, J=9.6, 4.1 Hz); ESIMS m/z 262 ([M+H]⁺).

Preparation 39:2-(7-Fluorobenzofuran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

2-(7-Fluorobenzofuran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane wasprepared as described in Preparation 98 from 6-bromo-7-fluorobenzofuran.¹H NMR (400 MHz, CDCl₃) δ 7.68 (t, J=3.1 Hz, 1H), 7.55 (dd, J=7.8, 4.5Hz, 1H), 7.34 (t, J=6.5 Hz, 1H), 6.80 (dd, J=2.9, 2.2 Hz, 1H), 1.38 (s,12H); ¹⁹F NMR (376 MHz, CDCl₃) δ −127.62 (dd, J=4.2, 3.1 Hz); ESIMS m/z262 ([M+H]⁺).

Preparation 40:2-(6-Fluorobenzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneand2-(4-fluorobenzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

2-(6-Fluorobenzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneand2-(4-fluorobenzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolanewere prepared as described in Preparation 98 from5-bromo-4-fluorobenzo[b]thiophene and 5-bromo-6-fluorobenzo[b]thiophene:¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, J=5.5 Hz, 1H), 7.53 (d, J=9.3 Hz,1H), 7.35 (d, J=5.5 Hz, 1H), 7.30 (d, J=5.5 Hz, 1H), 1.39 (s, 12H); ¹HNMR (400 MHz, CDCl₃) δ 7.69-7.61 (m, 2H), 7.47 (d, J=5.6 Hz, 1H), 7.39(d, J=5.6 Hz, 1H), 1.39 (s, 12H); ¹⁹F NMR (376 MHz, CDCl₃) δ −107.24,−109.56; ESIMS m/z 278 ([M+H]⁺).

Preparation 41:2-(5-Fluorobenzo[b]thiophen-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneand2-(5-fluorobenzo[b]thiophen-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

2-(5-Fluorobenzo[b]thiophen-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneand2-(5-fluorobenzo[b]thiophen-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolanewere prepared as described in Preparation 98 from6-bromo-5-fluorobenzo[b]thiophene and 4-bromo-5-fluorobenzo[b]thiophene:¹H NMR (400 MHz, CDCl₃) δ 8.26 (d, J=5.1 Hz, 1H), 7.59 (d, J=5.4 Hz,1H), 7.45 (d, J=9.9 Hz, 1H), 7.28 (d, J=5.4 Hz, 1H), 1.39 (s, 12H); ¹HNMR (400 MHz, CDCl₃) δ 7.92 (d, J=5.5 Hz, 1H), 7.88 (dd, J=8.8, 4.9 Hz,1H), 7.55 (d, J=5.5 Hz, 1H), 7.07 (t, J=9.1 Hz, 1H), 1.42 (s, 12H); ¹⁹FNMR (376 MHz, CDCl₃) δ −107.32, −107.34, −107.35, −107.36, −111.00,−111.02, −111.02, −111.03, −111.04, −111.04; ESIMS m/z 278 ([M+H]⁺).

Preparation 42:2-(Benzo[b]thiophen-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

6-Bromobenzo[b]thiophene (3.09 g, 14.5 mmol),4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (4.42 g,17.4 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-palladium(II)chloride (0.54 g, 0.74 mmol), and potassium acetate (2.89 g, 29.4 mmol)in anhydrous dioxane (48 mL) was refluxed at 80° C. for 4 h. Thereaction was cooled and diluted with ethyl acetate, filtered through apad of Celite, and washed with brine. The aqueous layer was extractedwith ethyl acetate. The organic layers were dried, filtered, andadsorbed onto silica gel. Purification by flash chromatography (0-30%ethyl acetate/hexanes) provided2-(benzo[b]thiophen-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as ayellow oily solid: (3.266 g, 87%): ¹H NMR (400 MHz, CDCl₃) δ 8.38 (d,J=0.7 Hz, 1H), 7.79 (ddd, J=20.2, 8.0, 0.8 Hz, 2H), 7.51 (d, J=5.5 Hz,1H), 7.34 (dd, J=5.4, 0.7 Hz, 1H), 1.37 (s, 12H); ¹³C NMR (101 MHz,CDCl₃) δ 141.78, 129.75, 129.58, 128.18, 123.87, 122.94, 83.89, 24.92;EIMS m/z 260.

Preparation 43:5-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

To a round bottom flask,4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.424 g,5.61 mmol), [1,1¹-bis(diphenylphosphino)ferrocene] dichloropalladium(II)(0.342 g, 0.467 mmol), and potassium acetate (0.917 g, 9.34 mmol) werecharged as solids. The flask was sealed, and pumped and purged 3× withinert gas. Then 6-bromo-5-fluoro-1H-indole (1.0 g, 4.67 mmol) in dioxane(15.57 mL) was added. The reaction was stirred and warmed to an internaltemperature of 85° C. After 18 h the reaction mixture was cooled andfiltered through a pad of Celite, washing with excess ethyl acetate. Thefiltrate was diluted with water and partitioned. The aqueous layer wasextracted with ethyl acetate (3×15 mL). The combined organics were driedover MgSO₄, filtered and concentrated in vacuo. The crude product waspurified using a Teledyne ISCO purification system with a gradienteluent system of ethyl acetate and hexanes to yield the title compoundas a peach-colored solid (656 mg, 54%): ¹H NMR (400 MHz, DMSO-d-₆) δ1.31 (s, 12H), 6.42 (ddd, J=2.9, 1.9, 0.9 Hz, 1H), 7.22 (d, J=10.5 Hz,1H), 7.52 (t, J=2.8 Hz, 1H), 7.69 (d, J=4.8 Hz, 1H), 11.24 (s, 1H); ¹⁹FNMR (376 MHz, DMSO-d₆) δ −116.07; ESIMS m/z 262.0 ([M+H]⁺), 260.0([M−H]⁻).

Preparation 44: 7-Bromo-4-chloro-1H-indole

To a solution of 1-bromo-4-chloro-2-nitrobenzene (932 mg, 3.95 mmol) intetrahydrofuran (10 mL), vinylmagnesium bromide (0.7 M intetrahydrofuran) (12 mmol) in tetrahydrofuran (15 mL) was added dropwise at −40° C. After 1 h the reaction mixture was poured into saturatedNH₄Cl. The resulting organic layer was concentrated. The resultingresidue was purified using a Teledyne ISCO chromatography system with agradient eluent system of 2% ethyl acetate in hexane to yield the titlecompound (400 mg, 44%): ¹H NMR (300 MHz, CDCl₃) δ 6.73 (t, J=2.8 Hz,1H), 7.02 (d, J=8.1 Hz, 1H), 7.19-7.39 (m, 2H), 8.43 (s, 1H).

Preparation 45: 4-Bromo-7-chloro-1H-indole

4-Bromo-7-chloro-1H-indole was prepared from4-bromo-1-chloro-2-nitrobenzene as described in Preparation 114: ¹H NMR(300 MHz, CDCl₃) δ 6.49-6.74 (m, 1H), 7.07 (d, J=8.1 Hz, 1H), 7.15-7.42(m, 2H), 8.49 (s, 1H).

Preparation 46: 6-Bromo-7-fluoro-1H-indole

6-Bromo-7-fluoro-1H-indole was prepared from1-bromo-2-fluoro-3-nitrobenzene as described in Preparation 114 (250 mg,25.2%): ¹H NMR (300 MHz, CDCl₃) δ 6.52-6.62 (m, 1H), 7.13-7.34 (m, 3H),8.38 (s, 1H); ESIMS m/z 215.0 ([M+H]⁺).

Preparation 47 (Precursor Example 1):4-Chloro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

To a solution of 7-bromo-4-chloro-1H-indole (8 g, 0.03 mol) in dioxane;KOAc (9.8 g, 0.1 mol),dichloro[1,1′-bis(diphenylphosphino)ferrocene]-palladium(II) (2.19 g,0.003 mol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane)(13.2 g, 0.052 mol) were charged as solids. The reaction was placedunder inert atmosphere and the flask was sealed. The reaction was heatedto 100° C. for 16 h. The reaction was then treated with H₂O andextracted with ethyl acetate. The organic layer was partitioned andconcentrated. The resulting residue was purified using a Teledyne ISCOchromatography system with a gradient eluent system of ethyl acetate inHexane to yield the title compound (1.3 g, 15.6%): ¹H NMR (300 MHz,CDCl₃) δ 1.40 (s, 24H), 6.58-6.73 (m, 1H), 7.14 (d, J=7.6 Hz, 1H),7.28-7.36 (m, 1H), 7.56 (d, J=7.6 Hz, 1H), 9.34 (s, 1H).

Preparation 48:7-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

7-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole wasprepared as described in Preparation 117 from 4-bromo-7-chloro-1H-indole(4.2 g, 43.7%): ¹H NMR (300 MHz, CDCl₃) δ 1.38 (s, 26H), 7.08 (dd,J=3.2, 2.2 Hz, 1H), 7.20 (d, J=7.6 Hz, 1H), 7.30 (t, J=2.8 Hz, 1H), 7.56(d, J=7.6 Hz, 1H), 8.40 (s, 1H).

Preparation 49 (Precursor Example 2):7-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole wasprepared as described in Preparation 117 from 6-bromo-7-fluoro-1H-indole(150 mg, 45.5%): ¹H NMR (300 MHz, CDCl₃) δ 1.26 (s, 25H), 1.39 (s, 24H),7.27 (d, J=4.5 Hz, 2H), 7.40 (d, J=2.6 Hz, 2H), 8.43 (s, 1H); ¹⁹F NMR(282 MHz, CDCl₃) δ −124.52; ¹³C NMR (101 MHz, CDCl₃) δ 24.87 (d, J=15.9Hz), 77.30, 83.49 (d, J=6.9 Hz), 103.25, 115.98 (d, J=3.3 Hz), 126.08(d, J=7.7 Hz).

Preparation 50 (Precursor Example 3):7-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole

7-Fluoro-1-(triisopropylsilyl)-1H-indole (4.0 g, 14 mmol) (Preparedaccording to M. Schlosser, et al, Eur. J. Org. Chem. 2006, 2956-2969)was dissolved in 30 mL dry THF, cooled to −75° C., treated in portionswith sec-butyl lithium (10 mL, 1.4 M, 14 mmol) and stirred for 2 h at−75° C. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.0 mL,2.7 g, 14 mmol) was added in portions and the mixture was stirred for 1h at −75° C. The cooling was removed and the temperature was allowed torise to 5° C. over 30 min. The reaction was quenched by addition of 5 mLsat. NH₄Cl and partitioned between ethyl acetate and water. The organicphase was washed with sat. NaCl, dried (Na₂SO₄), evaporated onto silicagel, and purified by flash chromatography (SiO₂; eluting with hexanes)to give 4.2 g of the title compound as a thick oil (4.2 g, 73%): ¹H NMR(400 MHz, CDCl3) δ 7.43 (dd, J=7.9, 4.6 Hz, 1H), 7.38 (m, 2H), 1.75 (m,3H), 1.38 (s, 12H), 1.13 (d, J=7.6 Hz, 18H). ¹⁹F NMR (376 MHz, CDCl3) δ−113.07. EIMS m/z 417.

Preparation 51: 2-Ethynyl-4,6-difluoroaniline

Step 1: 2-Bromo-4,6-difluoroaniline (10 g, 48 mmol), copper (I) iodide(180 mg, 0.96 mmol), bis(triphenylphosphine)palladium(II) chloride (680mg, 0.96 mmol) and ethynyltrimethylsilane (7.1 g, 72 mmol) were combinedwith 10 ml dry DMF and heated to 50° C. for 18 h. An additional 2 mLethynyltrimethylsilane, 200 mg bis(triphenylphosphine)palladium(II)chloride, and 60 mg CuI were added and heating was continued for 4 h.After cooling, the mixture was diluted with ethyl acetate and stirredwith 1 N HCl. The dark mixture was filtered through Celite to removefine solids. The organic phase was washed with water, sat. NaCl, driedand concentrated. Purification by flash chromatography (SiO₂, elutingwith 0-20% EtOAc in hexanes) afforded 9 g of material that consisted ofa 70/30 ratio of the TMS alkyne derivative and the starting bromide.

Step 2: The mixture was carried in to the desilylation without furtherpurification. The TMS derivative was dissolved in methanol (500 mL) andtreated with 8.5 g KF. A clear solution formed which was stirredovernight at RT. Most of the volatiles were removed under vacuum, theresidue was taken up in ethyl acetate and washed water and with sat.NaCl. The solution was dried, evaporated and purified by flashchromatography (SiO₂, eluting with 0-10% ethyl acetate in hexanes) toprovide the title compound (4.2 g, 70 area % pure by FID-GC): ¹H NMR(400 MHz, CDCl3) δ 6.83 (m, 1H), 4.13 (m, 1H), 3.46 (s, 1H). ¹⁹F NMR(376 MHz, CDCl3) δ −124.04, −124.88, −126.94, −130.08. EIMS m/z 153.This material was carried through to the cyclization step withoutfurther purification.

Preparation 52: 5,7-Difluoro-1H-indole

The impure 2-ethynyl-4,6-difluoroaniline (4.2 g, 19 mmol) from theprevious example was dissolved in ethanol (75 mL), treated with sodiumgold(III) chloride dihydrate (310 mg, 0.77 mmol) and stirred for 3 hunder an atmosphere of nitrogen. The mixture was concentrated, taken upin ethyl acetate, washed with water, washed with sat. NaCl, dried oversodium sulfate (Na₂SO₄) and evaporated. Purification by flashchromatography (SiO₂, 100-200 mesh; eluting with 0-15% EtOAc in hexanescontaining 2% acetic acid) provided of the title product (2.0 g, ca 85%purity): ¹H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.26 (dd, J=4.8, 2.0Hz, 1H), 7.09 (dd, J=9.1, 2.2 Hz, 1H), 6.74 (ddd, J=11.2, 9.3, 2.0 Hz,1H), 6.55 (td, J=3.3, 2.2 Hz, 1H). ¹⁹F NMR (376 MHz, CDCl3) δ −122.11,−131.96. EIMS m/z 153.

Preparation 53: 5,7-Difluoro-1-(triisopropylsilyl)-1H-indole

N-butyl lithium (2.7m1, 2.5 M, 6.9 mmol) was added to 10 mL dry THF at−70° C. 5,7-difluoro-1H-indole (1.0 g, 6.5 mmol) in 5 mL THF was addedin portions to the this solution and the mixture was stirred for 30 minat −75° C. Triisopropylchlorosilane (1.5 mL, 1.3 g, 6.9 mmol) was added,stirring was continued for 1 h at −75° C. and then the mixture wasallowed to warm to −5° C. over 2 h. After treatment with 5 mL sat.NH₄Cl, the mixture was mixed with 30 mL ether and the organic phase waswashed with 5 mL sat. NaCl, dried (Na₂SO₄) and evaporated. The productwas purified by flash chromatography(SiO₂; hexanes) to provide the titlecompound as a clear oil (1.5 g; 74%): ¹H NMR (400 MHz, CDCl3) δ 7.35 (d,J=3.1 Hz, 1H), 7.07 (dd, J=8.7, 2.3 Hz, 1H), 6.69 (m, 1H), 6.59(t, J=3.1Hz, 1H), 1.67 (m, 3H), 1.13 (d, J=7.6 Hz, 18H). 19F NMR (376 MHz, CDCl3)δ −120.64, −120.65, −122.49, −122.49. EIMS m/z 309.

Preparation 54: 5,7-Difluoro-6-iodo-1-(triisopropylsilyl)-1H-indole

5,7-difluoro-1-(triisopropylsilyl)-1H-indole (1.4 g, 4.5 mmol) andpentamethyldiethylene -triamine(830 mg, 4.8 mmol) were combined in 10 mLdry THF, cooled to −70° C. and treated in portions with sec-butyllithium (3.4 mL, 1.4 M, 4.8 mmol) and stirred for 3 h at thistemperature. Iodine (1.3 g, 5.0 mmol) in 5 mL THF was added, the mixturewas stirred for 50 min, quenched by addition of 3 mL sat. NH₄Cl andpartitioned between diethyl ether and water. The organic phase waswashed with sat. NaCl, dried (Na₂SO₄), evaporated and purified by flashchromatography (SiO₂; hexanes) the title compound as a clear oil whichsolidified on standing (1.9 g, 90%). ¹H NMR (400 MHz, CDCl3) δ 7.34 (d,J=3.1 Hz, 1H), 7.14 (dd, J=7.7, 0.9 Hz, 1H), 6.60 (t, J=3.1 Hz, 1H),1.67 (m, 3H), 1.13 (d, J=7.6 Hz, 18H). ¹⁹F NMR (376 MHz, CDCl3) δ−101.37, −105.33. MP: 74-76° C.

EXAMPLES OF SYNTHESIS OF COMPOUNDS OF FORMULA (I) Example 1 Methyl4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinate (CompoundNo. 1.14)

Methyl 4-amino-3,6-dichloro-5-fluoropicolinate (0.650 g, 2.72 mmol),7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole(0.817 g, 3.13 mmol), bis(triphenylphosphine)palladium(II) chloride(0.191 g, 0.272 mmol), and cesium fluoride (0.826 g, 5.44 mmol, Note:potassium fluoride replaced cesium fluoride in some examples that referto this particular example) were combined in acetonitrile (4.53 mL) andwater (4.53 mL). The reaction mixture was irradiated in a BiotageInitiator microwave at 110° C. in a sealed vial for 30 min. The cooledreaction mixture was partitioned between ethyl acetate and water. Theorganic phase was dried and concentrated. The product was purified byflash chromatography (SiO₂; eluting with 5-40% ethyl acetate in hexanes)to provide the title compound as an white solid (0.517 g, 52.4% yield).

The preparation method used in this example is referred to in Table 11as “Coupling 1.”

Example 2 Methyl 4-amino-3-chloro-5-fluoro-6-(1H-indol-5-yl)picolinate(Compound No. 1.2)

1H-Indol-5-ylboronic acid (220 mg, 1.4 mmol, 1.1 equiv) and methyl4-amino-3,6-dichloro-5-fluoropicolinate (300 mg, 1.3 mmol, 1.0 equiv)were sequentially added to a 5 mL Biotage microwave vessel, followed bycesium fluoride (380 mg, 2.5 mmol, 2.0 equiv), palladium(II) acetate (14mg, 0.063 mmol, 0.05 equiv), and sodium3,3′,3″-phosphinetriyltribenzenesulfonate (71 mg, 0.13 mmol, 0.10equiv). A 3:1 mixture of water:acetonitrile (2.5 mL) was added and theresulting dark brown mixture was placed in a Biotage microwave andheated to 150° C. for 5 m, with external IR-sensor temperaturemonitoring from the side of the vessel. The cooled reaction mixture wasdiluted with water (50 mL) and extracted with dichloromethane (15×30mL). The combined organic layers were dried (sodium sulfate), gravityfiltered, and concentrated by rotary evaporation. The residue waspurified by reverse phase column chromatography (5% acetonitrile to 100%acetonitrile gradient) to yield the title compound as a tan powder (290mg, 73%).

The preparation method used in this example is referred to in Table 11as “Coupling 2.”

Example 3 Methyl4-amino-6-(benzo[d]thiazol-5-yl)-3-chloro-5-fluoropicolinate (CompoundNo. 6.1)

To a 5 mL microwave vial was added methyl4-amino-6-bromo-3-chloro-5-fluoropicolinate (200 mg, 1.0 mmol),benzo[d]thiazol-5-ylboronic acid (237 mg, 1.35 mmol), potassium fluoride(KF; 122 mg, 2.12 mmol), TPPTS-Na(tris-(3-sulfornatophenyl)-phosphine4-hydrate sodium salt, 67 mg, 0.106mmol) and Pd(OAc)₂ (11 mg, 0.053 mmol). Subsequently, CH₃CN (1.0 mL) andH₂O (3.0 mL) were added, and the reaction vial was sealed and heated ina Biotage microwave at 150° C. for 5 min, with external IR-sensortemperature monitoring from the side of the vessel. The reaction mixturewas cooled to room temperature and diluted with dicloromethane, andwashed with water. The organic extracts were combined, dried (Na₂SO₄),filtered, and concentrated in vacuo. The crude product was purified bytriturating with Et₂O to yield the title compound as a brown solid (172mg, 51%).

The preparation method used in this example is referred to in Table 11as “Coupling 3.”

Example 4 Methyl4-amino-6-(benzo[b]thiophenyl-5-yl)-3,5-dichloropicolinate (Compound No.3.1)

To a 5 mL microwave vial was added methyl4-amino-3,5,6-trichloropicolinate (0.232 g, 0.909 mmol),2-(benzo[b]thiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.260g, 0.999 mmol), cesium fluoride (0.276 g, 1.817 mmol) and (PPh₃)₂PdCl₂(0.064 g, 0.091 mmol). The reaction vial was then sealed and placedunder inert atmosphere. Subsequently, Dioxane (4.0 mL) and H₂O (1.0 mL)were added and the reaction mixture was heated in a Biotage microwave at120° C. for 60 min, with external IR-sensor temperature monitoring fromthe side of the vessel. The reaction mixture was cooled to roomtemperature and diluted with ethyl acetate (5 mL) and poured into brinesolution. The layers were separated and the aqueous phase was extractedwith ethyl acetate (3×10 mL). The organic extracts were combined, dried(MgSO₄), filtered, and concentrated in vacuo. The crude product waspurified using a Teledyne ISCO purification system with a gradienteluent system of ethyl acetate and hexanes. Further purification wasperformed, as needed, using a Teledyne ISCO reverse phase system with agradient eluent system of acetonitrile and H₂O to yield the titlecompound as a white solid.

The preparation method used in this example is referred to in Table 11as “Coupling 4.”

Example 5 Methyl4-amino-3-chloro-6-(7-chlorobenzofuran-4-yl)-5-fluoropicolinate(Compound No. 2.16)

Combined potassium fluoride (0.365 g, 6.28 mmol), diacetoxypalladium(0.047 g, 0.209 mmol), and2-(7-chlorobenzofuran-4-yl)-5,5-dimethyl-1,3,2-dioxaborinane (0.609 g,2.301 mmol), sodium 3,3′,3″-phosphinetriyltribenzenesulfonatetetrahydrate (0.134 g, 0.209 mmol), methyl4-amino-3,6-dichloro-5-fluoropicolinate (0.5 g, 2.092 mmol). Added water(3 mL) and acetonitrile (1 mL). Heated reaction mixture at 150° C. in amicrowave reactor for 6 minutes. Diluted cooled reaction mixture withethyl acetate and water and filtered through cotton plug. Dried organicphase (Na₂SO₄) and concentrated under vacuum. Purified by reverse phasechromatography to provide the title compound as a white solid (127 mg,12.5% yield).

The preparation method used in this example is referred to in Table 11as “Coupling 5.”

Example 6 Methyl 4-amino-3-chloro-6-(7-fluoro-1H-indol-6-yl)picolinate(Compound No. 1.22)

Methyl 4-acetamido-3,6-dichloropicolinate (400 mg, 1.520mmol),7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole(437 mg, 1.673 mmol), cesium fluoride (462 mg, 3.04 mmol), and(PPh₃)₂PdCl₂ (107 mg, 0.152 mmol) were charged as solids into amicrowave reaction vessel and dioxane (4 mL) and water (1 mL) wereadded. The reaction vessel sealed and irradiated in a Biotage Initiatormicrowave at 110° C. for 2 h, with external IR-sensor temperaturemonitoring from the side. The reaction mixture was partitioned betweenethyl acetate and water. The organic phase was filtered andconcentrated. The intermediate product was purified by flashchromatography (ISCO 40 g silica 10-75% EtOAc: Hex 16 CV). Fractionscontaining product were combined and concentrated to give 524 mg of awhite solid intermediate methyl4-acetamido-3-chloro-6-(7-fluoro-1H-indol-6-yl)picolinate (0.524 g,1.448 mmol) which was subsequently diluted with methanol (10.0 mL).Thenacetyl chloride (0.725 mL, 10.20 mmol) was added. The reaction mixturewas allowed to stir at room temperature for 18 h. The reaction wasconcentrated to dryness. The resulting residue was dissolved in ethylacetate and poured into saturated NaHCO₃ solution. The layers werepartitioned and the aqueous layer was extracted with ethyl acetate (3×15mL). The organic extracts were combined, washed with saturated NaClsolution, dried (MgSO₄), filtered and concentrated in vacuo. The crudeproduct was purified using a Teledyne ISCO purification system with agradient eluent system of ethyl acetate and hexanes to yield the titlecompound as a white solid (365 mg, 79%).

The preparation method used in this example is referred to in Table 11as “Coupling 6.”

Example 7 Methyl4-amino-3-chloro-6-(5,7-difluoro-1H-indol-6-yl)picolinate (Compound No.1.26)

5,7-difluoro-6-iodo-1-(triisopropylsilyl)-1H-indole (450 mg, 1.0 mmol),methyl 4-acetamido-3-chloro-6-(trimethylstannyl)picolinate (450 mg, 1.1mmol) were combined in 7 mL dry DMF, deaerated with a stream of nitrogenfor 15 min, treated with bis(triphenylphosphine)palladium(II) chloride(72 mg, 0.10 mmol) and copper (I) iodide and heated to 60° C. for 2 h.The mixture was partitioned between ethyl acetate and water. The organicphase was washed with water, washed with sat. NaCl, dried (Na₂SO₄), andevaporated. Purification by flash chromatography (SiO₂, 100-200 mesh;eluting with 0-30% EtOAc in hexanes) provide 200 mg of the silylatedN-acetamide product. This material was slurried in methanol (15 mL),treated with 2 mL acetyl chloride and heated at reflux for 2 h. Thevolatiles were removed under vacuum and the residue was purified byflash chromatography (SiO₂; 0-40% ethyl acetate in hexanes) to provide30 mg of the title compound plus 60 mg of title compound that was stillprotected by the TIPS group on the indole nitrogen. The TIPS derivativewas dissolved in 5 mL dry THF, treated with tetrabutylammonium fluoridehydrate (140 mg, 0.5 mmol) and stirred for 1 h at 20° C. The mixture waspartitioned between 20 ml ethyl acetate and sat. NaCl. The organic phasewas dried (Na₂SO₄) and evaporated. Purification by flash chromatography(SiO₂; 0-50% ethyl acetate in hexanes) provide another 30 mg of thetitle compound as a white solid (60 mg, 16%).

The preparation method used in this example is referred to in Table 11as “Coupling 7.”

Example 8 Methyl4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinate (CompoundNo. 1.14)

7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole(500 mg, 1.2 mmol), methyl 4-amino-3,6-dichloro-5-fluoropicolinate (290mg, 1.2 mmol), cesium fluoride (360 mg, 2.4 mmol) andbis(triphenylphosphine)palladium(II) chloride (84 mg, 0.12 mmol) werecombined in 4 mL of a 1:1 v/v acetonitrile-water and heated at 115° C.for 25 min in a Biotage Initiator microwave reactor. The mixture waspartitioned between ethyl acetate and sat. NaCl and the organic phasewas dried and evaporated. Purification by flash chromatography (SiO₂;eluting with 0-20% ethyl acetate in dichloromethane) provided impureproduct. The material was purified by flash chromatography again (SiO₂;eluting with 0-30% ethyl acetate in hexanes) to provide the titlecompound as a white solid (220 mg, 52%).

The preparation method used in this example is referred to in Table 11as “Coupling 8.”

Example 9 Methyl4-amino-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-3-vinylpicolinate (CompoundNo. 1.17)

7-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole(320 mg, 0.77 mmol), methyl 4-amino-6-chloro-5-fluoro-3-vinylpicolinate(190 mg,0.84 mmol), sodium carbonate (81 mg, 0.77 mmol) andbis(triphenylphosphine)palladium(II) chloride (54 mg, 0.08 mmol) werecombined in 4 mL of a 1:1 v/v acetonitrile-water and heated to 115° C.for 30 min in a Biotage Initiator microwave reactor. The mixture waspartitioned between ethyl acetate and water. The organic phase waswashed with sat. NaCl, dried (Na₂SO₄), and evaporated. Purification byflash chromatography(SiO₂; eluting with 0-20% ethyl acetate in hexanes)provided 220 mg of the TIPS protected product. This material wasdissolved in 10 mL THF, treated with tetrabutylammonium fluoride hydrate(260 mg, 1.0 mmol) and stirred for 1 h. The mixture was partitionedbetween sat. NaCl and ethyl acetate. The organic phase was washed withsat. NaCl, dried (Na₂SO₄), and evaporated. Purification by flashchromatography (SiO₂; eluting with 0-20% ethyl acetate in hexanes)provided to give 100 mg of the title compound as a white solid (100 mg,37%).

The preparation method used in this example is referred to in Table 11as “Coupling 9.”

Example 10 Preparation of methyl4-amino-3-chloro-5-fluoro-6-(7-fluoro-1-(triisopropylsilyl)-1H-indol-6-yl)picolinate(Compound 1.12)

7-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole(1.0 g, 2.4 mmol), methyl 4-amino-3,6-dichloro-5-fluoropicolinate (630mg, 2.6 mmol), sodium carbonate (250 mg, 2.4 mmol) and withbis(triphenylphosphine)palladium(II) chloride (170 mg, 0.24 mmol) werecombined in 10 mL of 1:1 v/v acetonitrile-water and heated at 110° C.for 30 min in a Biotage Initiator microwave reactor. The mixture wasstirred with 30 mL ethyl acetate and 20 mL water and filtered throughglass wool to remove dark solids. The organic phase was washed with sat.NaCl, dried (Na₂SO₄), and evaporated. Purification by flashchromatography (SiO₂; eluting with 0-30% ethyl acetate in hexanes)provided 520 mg of the title compound as a white solid (520 mg; 42).

The preparation method used in this example is referred to in Table 11as “Coupling 10.”

Example 11 Methyl4-amino-6-(3-bromobenzo[b]thiophen-7-yl)-3-chloro-5-fluoropicolinate(Compound No. 3.26)

Methyl 4-amino-6-(benzo[b]thiophen-7-yl)-3-chloro-5-fluoropicolinate(0.500 g, 1.485 mmol) was dissolved in dichloromethane (9.90 mL) andcooled to −5° C. in a acetone bath to which was added a few pieces ofdry ice. Bromine (114 mL, 2.227 mmol) was dissolved in dichloromethane(9.90 mL) and added dropwise. The reaction mixture was stirredovernight, and then partitioned between ethyl acetate and water. Theorganic phase was dried and concentrated and the product purified byflash chromatography (SiO₂, 5-40% ethyl acetate/hexane gradient)followed by a second purification by reverse phase chromatography toprovide the title compound as a grey solid (0.278 g, 45).

Example 12 4-Amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinicacid (Compound 1.38)

To a reaction vessel containing methyl4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinate (0.500 g,1.481 mmol) was added methanol (14.81 ml) and sodium hydroxide (2.96 ml,5.92 mmol). The reaction mixture was stirred overnight at rt thenacidified by adding a slight excess of 2N HCl. The mixture wasconcentrated and the precipitate that formed was washed with water anddried under vacuum to provide4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)picolinic acid(0.400 g, 1.174 mmol, 79% yield) as an off-white solid:

The preparation method used in this example is referred to in Table 11as “Hydrolysis 1.”

Example 13 4-Amino-6-(benzo[b]thiophen-5-yl)-3,5-dichloropicolinic acid(Compound 3.2)

In a 100 mL round bottom flask, methyl4-amino-6-(benzo[b]thiophen-5-yl)-3,5-dichloropicolinate (210 mg, 0.595mmol) was dissolved in methanol (2.3 mL), tetrahydrofuran (2.3 mL), andH₂O (1.2 mL). Lithium hydroxide hydrate (74.8 mg, 1.784 mmol) was addedas a solid. The reaction was stirred at room temperature until complete.The reaction mixture was concentrated to dryness. The resulting residuewas dissolved in H₂O (2.0 mL) and 1 N HCl was used to adjust the pH to3.0, causing a precipitate to form. This suspension was extracted withethyl acetate (3×15 mL). The organic extracts were combined, washed withSaturated NaCl solution, dried (MgSO₄), filtered and concentrated.Additional purification of the resulting solid was performed, as needed,using a Teledyne ISCO reverse phase system with a gradient eluent systemof acetonitrile and H₂O to yield the title compound as a white solid(110 mg, 55.

The preparation method used in this example is referred to in Table 11as “Hydrolysis 2.”

TABLE 10 Compound Number, Structure, Appearance, and Preparation MethodCompound Preparation Number Structure Appearance Method: Precursor(s)1.01

White Powder Hydrolysis 1 Compound 1.03 1.02

Tan Powder Coupling 2 As described 1.03

White Powder Coupling 2 Head B; 1-Methyl-1H-indol- 5-ylboronic acid 1.04

Tan Powder Hydrolysis 1 Compound 1.02 1.05

Yellow Solid Coupling 1 Head H; (1H-indol-6- yl)boronic acid 1.06

Yellow Solid Hydrolysis 1 Compound 1.05 1.07

White solid Coupling 9 Head H 1.08

Off-White Foam Coupling 2 Head B; 1H-Indol-6- ylboronic acid 1.09

White Powder Hydrolysis 1 Compound 1.08 1.10

Tan Powder Coupling 2 Head B; 1-Methyl-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.11

Pale Yellow Powder Hydrolysis 1 Compound 1.10 1.12

White solid Coupling 10 Head B 1.13

Off White Solid Coupling 4 Head B; 5-fluoro-6-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)- 1H-indole 1.14

Tan Solid Hydrolysis 2 Compound 1.13 1.15

White Solid Coupling 4 Head B; 7-fluoro-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.16

Tan Solid Hydrolysis 2 Compound 1.15 1.17

White solid Hydrolysis 1 Compound 1.20 1.18

White solid Coupling 9 Head G 1.19

Tan solid Hydrolysis 1 Compound 1.18 1.20

White solid Coupling 8 Head F 1.21

White Solid Coupling 1 Head A, (1H-indol-6- yl)boronic acid 1.22

Orange Solid Hydrolysis 1 Compound 1.21 1.23

White Solid Coupling 6 As described 1.24

Yellow Solid Hydrolysis 2 Compound 1.23 1.25

White Solid Coupling 6 Head L; 5-fluoro-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-indole 1.26

White Solid Hydrolysis 2 Compound 1.25 1.27

White solid Coupling 7 Head K 1.28

Yellow Powder Coupling 1 Head D; (1H-indol-6- yl)boronic acid 1.29

Pale Pink Flaky Solid Hydrolysis 1 Compound 1.28 1.30

White solid Coupling 1 Head E 1.31

Yellow solid Coupling 8 Head E 1.32

White Solid Coupling 4 Head C; 6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.33

Yellow Solid Hydrolysis 2 Compound 1.32 1.34

White Solid Coupling 4 Head C; 7-fluoro-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.35

Yellow Solid Hydrolysis 2 Compound 1.34 1.36

White Solid Coupling 4 Head C; 5-fluoro-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.37

Yellow Solid Hydrolysis 2 Compound 1.36 1.38

Tan solid Coupling 8 Head P 1.39

Hydrolysis 1 Compound 1.38 1.40

White Solid Coupling 1 Head B; 4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.41

White Solid Coupling 1 Head B; 1-methyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.42

Off-White Solid Hydrolysis 1 Compound 1.41 1.43

White Solid Coupling 4 Head B; 7-chloro-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.44

Off White Solid Bottom of Form Coupling 6 Head L; 7-chloro-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan- 2-yl)-1H-indole 1.45

Off White Solid Coupling 4 Head C; 7-chloro-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)- 1H-indole 1.46

White Solid Coupling 4 Head B; 4-chloro-7-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.47

Off-White Solid Coupling 1 Head B; 7-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indole 1.48

Tan Solid Hydrolysis 1 Compound 1.47 1.49

Off White Solid Coupling 6 Head L; 4-chloro-7- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-indole 1.50

Off White Solid Coupling 4 Head C; 4-chloro-7-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)- 1H-indole 2.01

Yellow Solid 134 Head B; 2- (benzofuran-5-yl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2.02

White Solid Hydrolysis 1 Compound 2.01 2.03

yellow solid Coupling 1 Head L; benzofuran-5- ylboronic acid 2.04

Off-White Solid Coupling 1 Head A; 2-(6- fluorobenzofuran-5-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 2.05

White Solid Coupling 1 Head C; 2-(6- fluorobenzofuran-5- yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 2.06

Lt Yellow Oil At Room Temp Coupling 1 Head C; benzofuran- 5-boronic acid2.07

White Solid 134 Head B; 2- (benzofuran-6-yl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2.08

Off White Solid Hydrolysis 1 Compound 2.07 2.09

Light Yellow Solid Coupling 1 Head B; 2-(7- fluorobenzofuran-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 2.10

White Solid Coupling 1 Head B; 2-(5- fluorobenzofuran-6- yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 2.11

Off-White Solid Coupling 1 Head A; 2-(7- fluorobenzofuran-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 2.12

Beige Solid Coupling 1 Head A; 2-(5- fluorobenzofuran-6- yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 2.13

White Solid Coupling 1 Head C; 2-(7- fluorobenzofuran-6- yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 2.14

Off-White Solid Coupling 1 Head C; 2-(5- fluorobenzofuran-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 2.15

White Solid Coupling 5 Head B; 2- (benzofuran-4-yl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane 2.16

White Solid Coupling 5 Head B; 2-(7- chlorobenzofuran-4-yl)-5,5-dimethyl- 1,3,2-dioxaborinane 2.17

Tan Solid Hydrolysis 1 Compound 2.15 2.18

Off White Solid Hydrolysis 1 Compound 2.16 2.19

Light Yellow Solid Coupling 5 Head M; 2-(7- chlorobenzofuran-4-yl)-5,5-dimethyl- 1,3,2-dioxaborinane 2.20

Tan Solid Coupling 5 Head E; 2-(7- chlorobenzofuran-4- yl)-5,5-dimethyl-1,3,2-dioxaborinane 2.21

Tan Solid Coupling 5 Head C; 2-(7- chlorobenzofuran-4- yl)-5,5-dimethyl-1,3,2-dioxaborinane 2.22

Tan Solid Hydrolysis 1 Compound 2.21 2.23

Tan Solid Hydrolysis 1 Compound 2.20 2.24

Off-White Solid Coupling 1 Head B; 2-(4- chlorobenzofuran-7-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 2.25

Off-White Solid Coupling 1 Head A; 2-(4- chlorobenzofuran-7-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 2.26

Off-White Solid Coupling 1 Head C; 2-(4- chlorobenzofuran-7-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 3.01

White Solid Coupling 4 Head H; 2- (benzo[b]thiophen- 5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.02

White Solid Hydrolysis 2 Head H; 2- (benzo[b]thiophen- 5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.03

White Solid Coupling 2 Head B; 2- (benzo[b]thiophen- 5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.04

Tan Solid Hydrolysis 1 Compound 3.03 3.05

yellow solid Coupling 1 Head L; 2- (benzo[b]thiophen- 5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.06

Off-White Solid Coupling 1 Head D; 2- (benzo[b]thiophen- 5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.07

Off-White Solid Hydrolysis 1 Compound 3.06 3.08

White Solid Coupling 4 Head C; 2- (benzo[b]thiophen- 5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.09

White Solid Hydrolysis 2 Compound 3.08 3.10

White Solid Coupling 1 Head H; 2- (benzo[b]thiophen- 6-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.11

Yellow Solid Hydrolysis 1 Compound 3.10 3.12

Light Yellow Solid Coupling 5 Head B; 2- (benzothiophen-6- yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.13

Tan Solid Hydrolysis 1 Compound 3.12 3.14

Light Yellow Solid Coupling 1 Head B; 2-(5- fluorobenzothiophen-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 3.15

Off-White Brittle Solid Coupling 1 Head A; 2- (benzo[b]thiophen-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 3.16

White Solid Hydrolysis 1 Compound 3.15 3.17

White Solid Coupling 1 Head A; 2-(5- fluorobenzothiophen- 6-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.18

Yellow Solid Coupling 1 Head D; 2- (benzo[b]thiophen- 6-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane 3.19

Off-White Solid Hydrolysis 1 Compound 3.18 3.20

Light Yellow Solid Coupling 4 Head C; 2- (benzo[b]thiophen-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 3.21

White Solid Hydrolysis 2 Compound 3.20 3.22

Off-White Solid Coupling 1 Head C; 2-(5- fluorobenzothiophen-6-yl)-4,4,5,5- tetramethyl-1,3,2- dioxaborolane 3.23

White Solid Coupling 1 Head B; benzo[b]thiophen-4- ylboronic acid 3.24

White Solid Coupling 1 Head B; benzo[b]thiophen-7- ylboronic acid 3.25

White Solid Hydrolysis 1 Compound 3.24 3.26

Grey Solid 140 As described 3.27

yellow oil Coupling 1 Head L; benzo[b]thiophen-7- ylboronic acid 4.01

White Powder Coupling 2 Head B; 1H-Indazol-5- ylboronic acid 4.02

White Powder Hydrolysis 1 Compound 4.01 4.03

White Powder Coupling 2 Head B; 1-Methyl-1H- indazol-5-ylboronic acid4.04

White Powder Hydrolysis 1 Compound 4.03 4.05

White Powder Coupling 2 Head B; 1H-Indazol-6- ylboronic acid 4.06

Off-White Powder Hydrolysis 1 Compound 4.05 4.07

White Powder Coupling 2 Head B; 1-Methyl-1H- indazol-5-ylboronic acid4.08

White Powder Hydrolysis 1 Compound 4.07 4.09

White Solid Coupling 1 Head A; 1H-indazol-6- ylboronic acid 4.10

Yellow Solid Coupling 1 Head B; 1-methyl-4-(4,4,5,5-tetrameth^(y)l-1,3,2- dioxabor^(o)lan-2-yl)- 1H-indazole 4.11

Off-White Solid Hydrolysis 1 Compound 4.10 4.12

White Solid Coupling 1 Head B; 1H-indazol-4- ylboronic acid 4.13

White Solid Coupling 1 Head B; 7-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-indazole 5.01

Off White Solid Coupling 5 Head B; BENZOOXAZOLE- 5-BORONIC ACID PINACOLESTER 6.01

Light Brown Solid Coupling 3 As described 6.02

Light Brown Solid Hydrolysis 1 Compound 6.01 7.01

Off-White Powder Coupling 2 Head B; 6-(4,4,5,5- Tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H- benzo[d]imidazole 7.02

White Powder Coupling 2 Head B; 1-Methyl-1H- benzo[d]imidazol-6-ylboronic acid 7.03

White Powder Hydrolysis 1 Compound 7.02 8.01

Yellow Solid Coupling 1 Head B; N,N-dimethyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2- yl)benzo[d]isoxazol- 3-amine 9.01

White Solid Coupling 7 Head K; 6-bromo-1H- benzo[d][1,2,3] triazole

TABLE 11 Analytical Data for Compounds in Table 1 C. No. MP (° C.) HNMR1.01 166-168 ¹H NMR (300 MHz, DMSO-d₆) δ 8.06 (s, 1H), 7.67 (br d, J = 8Hz, 1H), 7.53 (d, J = 8 Hz, 1H), 7.39 (d, J = 3 Hz, 1H), 6.77 (br s,2H), 6.54 (d, J = 3 Hz, 1H), 3.83 (s, 3H) 1.02 221-224 ¹H NMR (300 MHz,DMSO-d₆) δ 8.04 (s, 1H), 7.59 (dt, J = 7, 1.5 Hz, 1H), 7.48 (d, J = 7Hz, 1H), 7.41 (t, J = 3 Hz, 1H), 6.85 (br s, 2H), 6.54 (m, 1H), 3.89 (s,3H) 1.03 125-127 ¹H NMR (300 MHz, DMSO-d₆) δ 8.21 (s, 1H), 7.82 (dt, J =9, 1.5 Hz, 1H), 7.39 (d, J = 9 Hz, 1H), 7.08 (d, J = 3 Hz, 1H), 6.56 (d,J = 3 Hz, 1H), 4.84 (br s, 2H), 3.99 (s, 3H), 3.82 (s, 3H) 1.04 180-182¹H NMR (300 MHz, DMSO-d₆) δ 11.26 (br s, 1H), 8.05 (s, 1H), 7.61 (dt, J= 9, 1.5 Hz, 1H), 7.48 (d, J = 9 Hz, 1H), 7.41 (t, J = 3 Hz, 1H), 7.67(br s, 2H), 6.54 (m, 1H) 1.05 174-179 ¹H NMR (400 MHz, CDCl₃) δ 8.50 (s,1H), 7.65 (d, J = 8.2 Hz, 2H), 7.40 (dd, J = 8.3, 1.4 Hz, 1H), 7.23-7.17(m, 1H), 6.54-6.48 (m, 1H), 5.30 (d, J = 3.9 Hz, 2H), 3.94 (s, 3H) 1.06160-164 ¹H NMR (400 MHz, DMSO-d₆) δ 13.64 (s, 1H), 11.26 (s, 1H),7.67-7.63 (m, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.48-7.41 (m, 1H), 7.25(dd, J = 8.2, 1.5 Hz, 1H), 6.89 (s, 2H), 6.48 (dd, J = 2.5, 1.5 Hz, 1H)1.07 185-190 ¹H NMR (400 MHz, DMSO) δ 11.79 (s, 1H), 7.94 (s, 2H), 7.55(m, 1H), 7.52 (m, 1H), 7.40 (d, J = 8.4 Hz, 1H), 6.55 (m, 1H), 3.93 (s,3H). ¹⁹F NMR (376 MHz, DMSO) δ −132.43. MP 185-190° C. ESIMS m/z 321[(M + H)+]. 1.08 66-69 ¹H NMR (300 MHz, CDCl₃) δ 8.31 (br s, 1H), 8.02(s, 1H), 7.71 (s, 2H), 7.29 (t, J = 3 Hz, 1H), 6.58 (m, 1H), 4.86 (br s,2H), 3.99 (s, 3H) 1.09 138-140 ¹H NMR (300 MHz, DMSO-d₆) δ 7.95 (s, 1H),7.63 (d, J = 8 Hz, 1H), 7.54 (dt, J = 8, 2 Hz, 1H), 7.47 (t, J = 3 Hz,1H), 6.79 (br s, 2H), 6.48 (m, 1H) 1.10 116-119 ¹H NMR (400 MHz, CDCl₃)δ 7.94 (t, J = 1 Hz, 1H), 7.69 (br s, 2H), 7.13 (d, J = 3 Hz, 1H), 6.50(dd, J = 3, 1 Hz, 1H), 4.85 (br s, 2H), 3.99 (s, 3H), 3.84 (s, 3H) 1.11173-176 ¹H NMR (400 MHz, DMSO-d₆) δ 7.93 (s, 1H), 7.66 (d, J = 8.5 Hz,1H), 7.59 (d, J = 8.5 Hz, 1H), 7.46 (d, J = 3 Hz, 1H), 6.50 (d, J = 3Hz, 1H), 6.37 (br s, 2H), 3.87 (s, 3H) 1.12 ¹H NMR (400 MHz, CDCl3) δ7.49 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 3.2 Hz, 1H), 7.29 (dd, J = 8.1,5.9 Hz, 1H), 4.90 (s, 2H), 3.98 (s, 3H), 1.68 (m, 3H), 1.14 (d, J = 7.6Hz, 18H). ¹⁹F NMR (376 MHz, CDCl3) δ −124.55, −124.65, −136.90, −137.00.MP: 181-182° C. ESIMS m/z 492 [(M − H)−]. 1.13 ¹H NMR (DMSO-d₆) δ 3.88(s, 3H), 6.49 (ddd, J = 2.9, 1.9, 0.8 Hz, 1H), 6.96 (s, 2H), 7.43 (d, J= 11.1 Hz, 1H), 7.50 (d, J = 6.0 Hz, 1H), 7.54 (t, J = 2.8 Hz, 1H),11.32 (s, 1H). 1.14 ¹H NMR (DMSO-d₆) δ 6.46-6.52 (m, 1H), 6.88 (s, 2H),7.42 (d, J = 11.1 Hz, 1H), 7.49-7.56 (m, 2H), 11.33 (s, 1H), 13.56 (s,1H). 1.15 ¹H NMR (DMSO-d₆) δ 3.88 (s, 3H), 6.59 (td, J = 3.2, 1.9 Hz,1H), 6.99 (s, 2H), 7.08 (dd, J = 8.2, 6.2 Hz, 1H), 7.47 (d, J = 8.2 Hz,1H), 7.52 (t, J = 2.8 Hz, 1H), 11.82 (t, J = 2.2 Hz, 1H). 1.16 ¹H NMR(DMSO-d₆) δ 6.59 (td, J = 3.2, 1.9 Hz, 1H), 6.90 (s, 2H), 7.10 (dd, J =8.2, 6.2 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 7.51 (t, J = 2.8 Hz, 1H),11.81 (s, 1H), 13.57 (s, 1H). 1.17 133-140 ¹H NMR (400 MHz, DMSO-d6) δ11.76 (s, 1H), 7.49 (dd, J = 3.0, 2.5 Hz, 1H), 7.44 (d, J = 7.9 Hz, 1H),7.09 (dd, J = 8.2, 6.2 Hz, 1H), 6.57 (td, J = 3.3, 1.9 Hz, 1H), 6.41 (s,2H), 3.80 (s, 3H). ¹⁹F NMR (376 MHz, DMSO) δ −134.66, −134.73. 133-140°C. ESIMS m/z 320 [(M + H)+]. 1.18 164-166 ¹H NMR (400 MHz, Chloroform-d)δ 8.45 (s, 1H), 7.49 (dd, J = 8.2, 0.8 Hz, 1H), 7.35-7.28 (m, 2H), 6.94(dd, J = 18.1, 11.5 Hz, 1H), 6.61 (td, J = 3.4, 2.1 Hz, 1H), 5.72 (dd, J= 11.5, 1.5 Hz, 1H), 5.60 (dd, J = 18.1, 1.5 Hz, 1H), 4.72 (s, 2H), 3.91(s, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ −135.79, −135.87, −140.98, −141.07.MP 164-166° C. ESIMS m/z 330 [(M + H)+]. 1.19 ¹H NMR (400 MHz, DMSO) δ11.76 (d, J = 16.4 Hz, 1H), 7.48 (m, 1H), 7.11 (dd, J = 8.2, 6.2 Hz,1H), 6.79 (dd, J = 17.8, 11.5 Hz, 1H), 6.58 (dd, J = 5.1, 3.2 Hz, 1H),6.38 (s, 1H), 5.56 (m, 1H). ¹⁹F NMR (376 MHz, DMSO) δ −134.07, −134.15,−143.26, −143.34. ESIMS m/z 316 [(M + H)+]. 1.20 203-205 ¹H NMR (400MHz, DMSO) δ 11.76 (s, 1H), 7.49 (dd, J = 6.0, 3.3 Hz, 1H), 7.44 (d, J =8.2 Hz, 1H), 7.05 (dd, J = 8.1, 6.3 Hz, 1H), 6.57 (m, 1H), 6.49 (s, 2H),3.84 (s, 3H), 3.79 (s, 3H). ¹⁹F NMR (376 MHz, DMSO) δ −134.75, −134.82,−138.34, −138.42. MP 203-205° C. ESIMS m/z 334 [(M + H)+]. 1.21 83-85 ¹HNMR (400 MHz, DMSO-d₆) δ 11.20 (s, 1H), 8.00 (m, 1H), 7.59 (m, 1H), 7.53(m, 1H), 7.43 (dd, J = 3.1, 2.4 Hz, 1H), 7.32 (s, 1H), 6.61 (s, 2H),6.45 (s, 1H), 3.91 (s, 3H) 1.22 172-174 ¹H NMR (400 MHz, DMSO-d6) δ11.47 (s, 1H), 7.94 (d, J = 1.2 Hz, 1H), 7.67 (d, J = 8.3 Hz, 2H), 7.52(t, J = 2.8 Hz, 1H), 7.46 (dd, J = 8.4, 1.7 Hz, 1H), 6.51 (t, J = 2.5Hz, 1H), NaN (m, 2H) 1.23 ¹H NMR (DMSO-d₆) δ 3.89 (s, 3H), 6.54 (td, J =3.4, 1.9 Hz, 1H), 6.75 (s, 2H), 7.31 (d, J = 1.5 Hz, 1H), 7.37-7.52 (m,3H), 11.76 (s, 1H). 1.24 ¹H NMR (DMSO-d₆) δ 6.50-6.62 (m, 1H), 6.71 (s,2H), 7.27 (d, J = 1.5 Hz, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.45-7.53 (m,2H), 11.76 (d, J = 2.4 Hz, 1H), 13.48 (s, 1H). 1.25 ¹H NMR (DMSO-d₆) δ3.90 (s, 3H), 6.45 (ddd, J = 2.9, 1.9, 0.9 Hz, 1H), 6.75 (s, 2H), 7.29(d, J = 1.7 Hz, 1H), 7.40 (d, J = 12.7 Hz, 1H), 7.52 (t, J = 2.8 Hz,1H), 7.93 (dd, J = 6.8, 0.8 Hz, 1H), 11.27 (t, J = 2.3 Hz, 1H). 1.26 ¹HNMR (DMSO-d₆) δ 6.45 (t, J = 2.4 Hz, 1H), 6.68 (s, 2H), 7.24 (d, J = 1.6Hz, 1H), 7.40 (d, J = 12.8 Hz, 1H), 7.52 (t, J = 2.8 Hz, 1H), 7.95 (d, J= 6.7 Hz, 1H), 11.29 (s, 1H), 13.54 (s, 1H). 1.27 169-171 ¹H NMR (400MHz, CDCl3) δ 8.45 (s, 1H), 7.29 (t, J = 2.7 Hz, 1H), 7.16 (d, J = 10.0Hz, 1H), 6.93 (dd, J = 1.5, 0.8 Hz, 1H), 6.54 (s, 1H), 4.82 (s, 2H),3.98 (s, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ −126.04, −135.41. MP: 169-171°C. ESIMS m/z 336 [(M − H)−]. 1.28 231-234 ¹H NMR (400 MHz, DMSO-d₆) δ11.15 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.42 (dd, J = 6.3, 3.6 Hz, 2H),7.05 (dd, J = 8.2, 1.5 Hz, 1H), 6.47 (dd, J = 2.5, 1.6 Hz, 1H), 6.39 (s,2H), 3.85 (s, 3H), 2.14 (s, 3H). 1.29 168-175 ¹H NMR (400 MHz, DMSO-d₆)δ 11.31 (s, 1H), 7.66-7.60 (m, 1H), 7.49 (s, 1H), 7.48-7.43 (m, 1H),7.07 (dt, J = 15.8, 7.9 Hz, 3H), 6.53-6.48 (m, 1H), 2.13 (s, 3H) 1.30240-242 ¹H NMR (400 MHz, DMSO-d₆) δ 11.33 (s, 1H), 8.37 (s, 1H), 7.96(dd, J = 8.4, 1.5 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.50 (m, 1H), 6.47(d, J = 1.1 Hz, 1H), 3.94 (s, 3H); ESIMS m/z 303 [(M + H)+]. 1.31185-190 ¹H NMR (400 MHz, DMSO) δ 11.79 (s, 1H), 7.94 (s, 2H), 7.55 (m,1H), 7.52 (m, 1H), 7.40 (d, J = 8.4 Hz, 1H), 6.55 (m, 1H), 3.93 (s, 3H).¹⁹F NMR (376 MHz, DMSO) δ −132.43. MP 185-190° C. ESIMS m/z 321 [(M +H)+]. 1.32 190-191 ¹H NMR (DMSO-d₆) δ 3.74 (s, 3H), 3.92 (s, 3H), 6.46(ddd, J = 3.0, 1.9, 0.9 Hz, 1H), 7.27 (s, 2H), 7.46 (t, J = 2.7 Hz, 1H),7.56 (d, J = 8.4 Hz, 1H), 7.94 (dd, J = 8.4, 1.5 Hz, 1H), 8.33 (d, J =1.1 Hz, 1H), 11.26 (d, J = 2.3 Hz, 1H). 1.33 154-157 ¹H NMR (DMSO-d₆) δ3.75 (s, 3H), 6.41-6.50 (m, 1H), 7.20 (s, 2H), 7.46 (t, J = 2.7 Hz, 1H),7.56 (d, J = 8.4 Hz, 1H), 7.96 (dd, J = 8.4, 1.5 Hz, 1H), 8.25-8.46 (m,1H), 11.27 (s, 1H). 1.34 ¹H NMR (DMSO-d₆) δ 3.75 (s, 3H), 3.90 (s, 3H),6.53 (td, J = 3.2, 1.9 Hz, 1H), 7.37 (d, J = 8.3 Hz, 3H), 7.44-7.54 (m,2H), 11.71 (s, 1H). 1.35 ¹H NMR (DMSO-d₆) δ 3.77 (s, 3H), 6.53 (td, J =3.2, 1.9 Hz, 1H), 7.12- 7.35 (m, 2H), 7.37 (d, J = 8.3 Hz, 1H),7.46-7.58 (m, 2H), 11.72 (t, J = 2.2 Hz, 1H), 13.49 (s, 1H). 1.36 ¹H NMR(DMSO-d₆) δ 3.76 (s, 3H), 3.89 (s, 3H), 6.44 (ddd, J = 3.0, 1.8, 0.9 Hz,1H), 7.32 (d, J = 11.9 Hz, 3H), 7.51 (t, J = 2.8 Hz, 1H), 7.85 (d, J =6.5 Hz, 1H), 11.30 (s, 1H). 1.37 ¹H NMR (DMSO-d₆) δ 3.75 (s, 3H), 6.43(ddd, J = 2.9, 1.9, 0.8 Hz, 1H), 7.10-7.46 (m, 3H), 7.50 (t, J = 2.7 Hz,1H), 7.85 (dd, J = 6.4, 0.8 Hz, 1H), 11.29 (t, J = 2.3 Hz, 1H), 13.48(s, 1H). 1.38 181-182 ¹H NMR (400 MHz, DMSO) δ 11.75 (s, 1H), 7.55 (dd,J = 8.3, 6.7 Hz, 1H), 7.50 (m, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.21 (s,1H), 6.67 (dd, J = 17.6, 11.5 Hz, 1H), 6.54 (dd, J = 5.1, 3.2 Hz, 1H),5.48 (ddd, J = 11.4, 7.3, 1.1 Hz, 1H), 3.83 (s, 1H), 3.33 (s, 1H). ¹⁹FNMR (376 MHz, DMSO) δ −132.89. MP 172-173° C. ESIMS m/z 313 [(M + H)+].1.39 209-211 ¹H NMR (400 MHz, DMSO) δ 13.51 (s, 1H), 11.75 (s, 1H), 7.56(m, 1H), 7.50 (t, J = 2.5 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.14 (s,1H), 6.67 (dd, J = 17.7, 11.5 Hz, 1H), 6.54 (s, 1H), 5.60 (d, J = 17.8Hz, 1H), 5.49 (d, J = 11.4 Hz, 1H). ¹⁹F NMR (376 MHz, DMSO) δ −132.98.MP: 209-211° C.. ESIMS m/z 299 [(M + H)+]. 1.40 233-236 ¹H NMR (400 MHz,CDCl₃) δ 8.27 (s, 1H), 7.51-7.45 (m, 2H), 7.32- 7.28 (m, 2H), 6.93-6.79(m, 1H), 4.90 (s, 2H), 3.98 (s, 3H) 1.41 167-169 ¹H NMR (400 MHz, CDCl₃)δ 7.46 (ddd, J = 7.3, 2.1, 0.8 Hz, 1H), 7.41 (d, J = 8.2 Hz, 1H),7.33-7.28 (m, 1H), 7.13 (d, J = 3.1 Hz, 1H), 6.79-6.68 (m, 1H), 4.89 (s,2H), 3.98 (s, 3H), 3.83 (s, 3H) 1.42 158-160 ¹H NMR (400 MHz, DMSO-d₆) δ7.55 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 3.1 Hz, 1H), 7.32-7.22 (m, 2H),6.77 (s, 2H), 6.50 (t, J = 2.3 Hz, 1H), 3.84 (s, 3H) 1.43 ¹H NMR(DMSO-d₆) δ 3.88 (s, 3H), 6.61 (dt, J = 3.1, 2.0 Hz, 1H), 6.95 (s, 2H),7.22-7.35 (m, 2H), 7.49 (t, J = 2.8 Hz, 1H), 11.65 (s, 1H). 1.44 116 ¹HNMR (DMSO-d₆) δ 3.91 (s, 3H), 6.74 (s, 2H), 6.97 (dd, J = 3.2, 1.8 Hz,1H), 7.28 (d, J = 8.0 Hz, 1H), 7.36 (s, 1H), 7.43 (d, J = 8.0 Hz, 1H),7.54 (t, J = 2.8 Hz, 1H), 11.65 (s, 1H). 1.45 226 ¹H NMR (DMSO-d₆) δ3.76 (s, 3H), 3.93 (s, 3H), 7.25 (d, J = 8.1 Hz, 1H), 7.34 (s, 2H), 7.49(t, J = 2.8 Hz, 1H), 7.59 (dd, J = 3.0, 2.0 Hz, 1H), 7.99 (d, J = 8.2Hz, 1H), 11.55 (s, 1H). 1.46 ¹H NMR (DMSO-d₆) δ 3.93 (s, 3H), 6.60 (dd,J = 3.2, 2.0 Hz, 1H), 7.03 (s, 2H), 7.24 (d, J = 8.0 Hz, 1H), 7.50 (dd,J = 8.0, 0.9 Hz, 1H), 7.55 (t, J = 2.8 Hz, 1H), 11.44 (s, 1H). 1.47 96-100 ¹H NMR (300 MHz, CDCl₃) δ 11.33 (s, 1H), 7.97 (d, J = 7.7 Hz,1H), 7.76 (d, J = 7.8 Hz, 1H), 7.37-7.29 (m, 1H), 7.18 (t, J = 7.7 Hz,1H), 6.65- 6.55 (m, 1H), 4.83 (s, 2H), 4.03 (s, 3H) 1.48 171-175 ¹H NMR(400 MHz, DMSO-d₆) δ 11.12 (s, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.51 (d, J= 7.4 Hz, 1H), 7.41 (t, J = 2.8 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.89(s, 2H), 6.53 (dd, J = 3.0, 2.1 Hz, 1H) 1.49 186-188 ¹H NMR (DMSO-d₆) δ3.96 (s, 3H), 6.57 (dd, J = 3.2, 2.2 Hz, 1H), 6.81 (s, 2H), 7.23 (d, J =8.0 Hz, 1H), 7.45 (s, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.55- 7.59 (m, 1H),11.51 (s, 1H). 1.50 147-149 ¹H NMR (DMSO-d₆) δ 3.78 (s, 3H), 3.94 (s,3H), 6.60 (dd, J = 3.2, 2.2 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H), 7.29-7.88(m, 3H), 8.09 (d, J = 8.2 Hz, 1H), 11.75 (s, 1H). 2.01 114-117 ¹H NMR(400 MHz, CDCl₃) δ 8.16 (t, J = 1.4 Hz, 1H), 7.87 (dt, J = 8.7, 1.8 Hz,1H), 7.66 (d, J = 2.2 Hz, 1H), 7.61-7.54 (m, 1H), 6.86-6.81 (m, 1H),4.90 (s, 2H), 4.00 (s, 3H). 2.02 165-167 ¹H NMR (400 MHz, DMSO-d₆) δ13.60 (s, 1H), 8.13 (s, 1H), 8.07 (d, J = 2.2 Hz, 1H), 7.80 (d, J = 8.7Hz, 1H), 7.75-7.64 (m, 1H), 7.07 (dd, J = 7.9, 6.5 Hz, 1H), 6.88 (s,2H). 2.03 84-87 ¹H NMR (400 MHz, DMSO-d₆) δ 3.90 (d, J = 3.3 Hz, 3H),6.75 (d, J = 19.2 Hz, 2H), 6.92-8.22 (m, 6H) 2.04  98 ¹H NMR (400 MHz,CDCl₃) δ 8.19 (d, J = 7.7 Hz, 1H), 7.63 (d, J = 2.2 Hz, 1H), 7.28 (d, J= 11.2 Hz, 1H), 7.22 (d, J = 2.0 Hz, 1H), 6.79 (dd, J = 2.2, 0.9 Hz,1H), 4.80 (s, 2H), 4.01 (s, 3H). 2.05 160 ¹H NMR (400 MHz, CDCl₃) δ 8.11(d, J = 7.4 Hz, 1H), 7.63 (d, J = 2.2 Hz, 1H), 7.29 (d, J = 10.6 Hz,1H), 6.78 (dd, J = 2.2, 0.9 Hz, 1H), 5.40 (s, 2H), 4.01 (s, 3H), 3.95(s, 3H). 2.06 ¹H NMR (400 MHz, CDCl₃) δ 8.20 (dd, J = 7.7, 0.8 Hz, 1H),7.79 (dd, J = 2.1, 0.9 Hz, 1H), 7.69 (d, J = 2.2 Hz, 1H), 7.62 (d, J =8.2 Hz, 1H), 6.79 (dd, J = 2.1, 1.0 Hz, 1H), 5.32 (s, 2H), 3.95 (s, 3H),3.93 (s, 3H). 2.07 ¹H NMR (400 MHz, CDCl₃) δ 8.10 (s, 1H), 7.88-7.83 (m,1H), 7.70 (t, J = 2.5 Hz, 1H), 7.69-7.66 (m, 1H), 6.81 (dd, J = 2.2, 1.0Hz, 1H), 4.91 (s, 2H), 4.00 (d, J = 1.5 Hz, 3H). 2.08 168-170 ¹H NMR(400 MHz, DMSO-d₆) δ 13.59 (s, 1H), 8.11 (d, J = 2.2 Hz, 1H), 8.03 (s,1H), 7.77 (s, 2H), 7.04 (dd, J = 2.1, 0.9 Hz, 1H), 6.90 (s, 2H). 2.09151 ¹H NMR (400 MHz, CDCl₃) δ 7.73 (d, J = 2.1 Hz, 1H), 7.48-7.41 (m,2H), 6.85 (s, 1H), 4.94 (s, 2H), 3.97 (d, J = 5.6 Hz, 3H). 2.10 109 ¹HNMR (400 MHz, CDCl₃) δ 7.72 (t, J = 3.3 Hz, 2H), 7.34 (dd, J = 9.5, 5.3Hz, 1H), 6.79 (dd, J = 2.2, 0.9 Hz, 1H), 4.93 (s, 2H), 3.98 (s, 3H).2.11 148 ¹H NMR (400 MHz, CDCl₃) δ 7.87 (dd, J = 8.2, 6.5 Hz, 1H), 7.71(d, J = 2.1 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H),6.82 (dd, J = 3.0, 2.2 Hz, 1H), 4.82 (s, 2H), 4.01 (s, 3H). 2.12 130 ¹HNMR (400 MHz, CDCl₃) δ 8.15 (d, J = 5.7 Hz, 1H), 7.70 (d, J = 2.2 Hz,1H), 7.35-7.28 (m, 2H), 6.75 (dd, J = 2.2, 0.9 Hz, 1H), 4.80 (s, 2H),4.01 (s, 3H). 2.13 178 ¹H NMR (400 MHz, CDCl₃) δ 7.82 (dd, J = 8.2, 6.3Hz, 1H), 7.71 (d, J = 2.1 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 6.84-6.75(m, 1H), 5.40 (s, 2H), 4.01 (s, 3H), 3.95 (s, 3H). 2.14 153 ¹H NMR (400MHz, CDCl₃) δ 8.06 (d, J = 5.9 Hz, 1H), 7.70 (t, J = 3.4 Hz, 1H), 7.32(d, J = 10.6 Hz, 1H), 6.75 (dd, J = 2.2, 0.9 Hz, 1H), 5.39 (s, 2H), 4.01(s, 3H), 3.96 (s, 3H). 2.15 100-103 ¹H NMR (400 MHz, CDCl₃) δ 7.72-7.69(m, 1H), 7.68-7.63 (m, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.42-7.36 (m, 1H),7.20-7.15 (m, 1H), 4.94 (s, 2H), 4.00 (d, J = 1.5 Hz, 3H). 2.16 184-186¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J = 2.2 Hz, 1H), 7.61 (dd, J = 8.2,2.1 Hz, 1H), 7.42-7.38 (m, 1H), 7.26-7.24 (m, 1H), 4.96 (s, 2H), 4.00(s, 3H). 2.17 170-173 ¹H NMR (400 MHz, DMSO-d₆) δ 13.63 (s, 1H), 8.07(d, J = 2.2 Hz, 1H), 7.72 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 7.5 Hz, 1H),7.44 (t, J = 7.9 Hz, 1H), 7.09 (s, 1H), 6.93 (s, 2H). 2.18 ¹H NMR (400MHz, CDCl₃) δ 7.81 (d, J = 2.3 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.45(d, J = 8.2 Hz, 1H), 6.96 (s, 1H), 5.20 (s, 2H). 2.19 158-159 ¹H NMR(400 MHz, DMSO-d₆) δ 8.24 (d, J = 2.1 Hz, 1H), 7.68 (d, J = 8.2 Hz, 1H),7.55 (d, J = 8.2 Hz, 1H), 7.50 (d, J = 2.1 Hz, 1H), 7.37 (s, 1H), 6.83(s, 2H), 3.93 (s, 3H). 2.20 ¹H NMR (400 MHz, CDCl₃) δ 8.22 (d, J = 8.3Hz, 1H), 7.79 (dd, J = 12.0, 2.1 Hz, 2H), 7.38 (d, J = 8.3 Hz, 1H), 5.61(s, 2H), 4.05 (s, 3H). 2.21 ¹H NMR (400 MHz, CDCl₃) δ 8.22-8.09 (m, 1H),7.86 (d, J = 2.1 Hz, 1H), 7.77 (d, J = 2.1 Hz, 1H), 7.42-7.34 (m, 1H),5.39 (s, 2H), 4.04 (s, 3H), 3.95 (s, 3H). 2.22 204-206 ¹H NMR (400 MHz,DMSO-d₆) δ 8.22 (d, J = 2.1 Hz, 1H), 8.20 (d, J = 8.3 Hz, 1H), 8.00 (d,J = 2.1 Hz, 1H), 7.52 (d, J = 8.3 Hz, 1H), 7.42 (s, 1H), 3.78 (s, 3H).2.23  173-174.5 ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J = 2.2 Hz, 1H), 7.61(dd, J = 8.2, 2.1 Hz, 1H), 7.42-7.38 (m, 1H), 7.26-7.24 (m, 1H), 4.96(s, 2H), 4.00 (s, 3H). 2.24 167 ¹H NMR (400 MHz, CDCl₃) δ 7.68 (d, J =2.2 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.37-7.34 (m, 1H), 6.93 (d, J =2.2 Hz, 1H), 4.95 (s, 2H), 3.99 (d, J = 4.7 Hz, 3H). 2.25 169 ¹H NMR(400 MHz, CDCl₃) δ 8.14 (d, J = 8.2 Hz, 1H), 7.75 (d, J = 10.0 Hz, 2H),7.34 (d, J = 8.3 Hz, 1H), 6.97 (t, J = 8.0 Hz, 1H), 4.86 (s, 2H), 4.02(s, 3H). 2.26 178 ¹H NMR (400 MHz, CDCl₃) δ 8.09 (d, J = 8.2 Hz, 1H),7.79 (d, J = 2.1 Hz, 1H), 7.32 (d, J = 8.3 Hz, 1H), 6.92 (d, J = 2.2 Hz,1H), 5.44 (s, 2H), 4.04 (s, 3H), 3.96 (s, 3H). 3.01 50-56 ¹H NMR(DMSO-d₆) δ 3.89 (s, 3H), 7.09 (s, 2H), 7.52-7.63 (m, 2H), 7.86 (d, J =5.4 Hz, 1H), 8.07-8.17 (m, 2H). 3.02 157-159 ¹H NMR (DMSO-d₆) δ 6.98 (s,2H), 7.53-7.61 (m, 2H), 7.84 (d, J = 5.5 Hz, 1H), 8.06-8.13 (m, 2H),13.70 (s, 1H). 3.03 84-85 ¹H NMR (400 MHz, DMSO-d₆) δ 8.34 (s, 1H), 8.12(d, J = 8.5 Hz, 1H), 7.87-7.78 (m, 2H), 7.60 (dd, J = 5.5, 0.6 Hz, 1H),6.95 (s, 2H), 3.90 (s, 3H) 3.04 149-150 ¹H NMR (400 MHz, DMSO-d₆) δ 8.36(s, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.83 (t, J = 6.1 Hz, 2H), 7.58 (d, J= 5.4 Hz, 1H), 6.71 (s, 2H); 3.05 142-144 ¹H NMR (400 MHz, DMSO-d₆) δ8.41 (d, J = 1.7 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.82-7.88 (m, 2H),7.51-7.72 (m, 3H), 7.39 (s, 1H), 3.92 (s, 3H) 3.06 155-159 ¹H NMR (400MHz, CDCl₃) δ 7.94-7.88 (m, 2H), 7.48 (d, J = 5.4 Hz, 1H), 7.41 (dd, J =8.3, 1.7 Hz, 1H), 7.36 (dd, J = 5.4, 0.6 Hz, 1H), 4.83 (s, 2H), 3.96 (s,3H), 2.19 (s, 3H) 3.07 159-165 ¹H NMR (400 MHz, DMSO-d₆) δ 8.10 (d, J =8.3 Hz, 1H), 7.97 (s, 1H), 7.85 (d, J = 5.4 Hz, 1H), 7.54 (d, J = 5.5Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 6.81 (s, 2H), 2.12 (s, 3H) 3.08125-127 ¹H NMR (DMSO-d₆) δ 3.76 (s, 3H), 3.92 (s, 3H), 7.40 (s, 2H),7.60 (dd, J = 5.4, 0.7 Hz, 1H), 7.81 (d, J = 5.4 Hz, 1H), 8.06 (d, J =8.6 Hz, 1H), 8.24 (dd, J = 8.5, 1.7 Hz, 1H), 8.73 (d, J = 1.5 Hz, 1H).3.09 137-139 ¹H NMR (DMSO-d₆) δ 3.76 (s, 3H), 7.31 (s, 2H), 7.59 (d, J =5.4 Hz, 1H), 7.81 (d, J = 5.4 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 8.26(dd, J = 8.5, 1.7 Hz, 1H), 8.76 (d, J = 1.5 Hz, 1H), 13.54 (s, 1H). 3.10134-135 ¹H NMR (400 MHz, CDCl₃) δ 8.22-8.09 (m, 1H), 7.87 (d, J = 8.2Hz, 1H), 7.66 (dd, J = 8.3, 1.6 Hz, 1H), 7.52 (d, J = 5.5 Hz, 1H), 7.36(dd, J = 5.5, 0.6 Hz, 1H), 5.34 (s, 2H), 3.97 (s, 3H) 3.11 239 ¹H NMR(400 MHz, DMSO-d₆) δ 8.22 (d, J = 0.7 Hz, 1H), 7.96 (d, J = 8.2 (dec)Hz, 1H), 7.88 (d, J = 5.4 Hz, 1H), 7.59 (dd, J = 8.3, 1.6 Hz, 1H), 7.53(d, J = 5.4 Hz, 1H), 7.02 (s, 2H) 3.12 185-189 ¹H NMR (400 MHz, CDCl₃) δ8.48 (s, 1H), 7.95 (dt, J = 8.4, 1.6 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H),7.54 (d, J = 5.4 Hz, 1H), 7.37 (d, J = 5.4 Hz, 1H), 4.91 (s, 2H), 4.01(s, 3H). 3.13 165-167 ¹H NMR (400 MHz, DMSO-d₆) δ 13.60 (s, 1H), 8.45(d, J = 6.7 Hz, 1H), 7.99 (t, J = 7.0 Hz, 1H), 7.88 (dd, J = 13.5, 6.4Hz, 2H), 7.52 (t, J = 4.7 Hz, 1H), 6.83 (d, J = 64.9 Hz, 2H). 3.14 112¹H NMR (400 MHz, CDCl₃) δ 8.08 (d, J = 6.2 Hz, 1H), 7.60 (d, J = 5.5 Hz,1H), 7.56 (s, 1H), 7.33 (s, 1H), 4.94 (s, 2H), 3.99 (s, 3H). 3.15 ¹H NMR(400 MHz, CDCl₃) δ 8.55−8.44 (m, 1H), 7.92-7.79 (m, 2H), 7.50 (d, J =5.4 Hz, 1H), 7.34 (dd, J = 5.4, 0.7 Hz, 1H), 7.17 (s, 1H), 4.82 (s, 2H),4.02 (s, 3H). 3.16 176-177 ¹H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H),8.60-8.51 (m, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.91 (dd, J = 8.4, 1.6 Hz,1H), 7.85 (d, J = 5.4 Hz, 1H), 7.51 (dd, J = 5.4, 0.6 Hz, 1H), 7.35 (s,1H), 6.69 (s, 2H). 3.17  70 ¹H NMR (400 MHz, CDCl₃) δ 8.53 (d, J = 7.0Hz, 1H), 7.58 (d, J = 5.5 Hz, 1H), 7.55 (d, J = 7.1 Hz, 1H), 7.52 (s,1H), 7.29 (d, J = 5.5 Hz, 1H), 4.81 (s, 2H), 4.02 (s, 3H). 3.18 143-146¹H NMR (400 MHz, CDCl₃) δ 8.01-7.94 (m, 1H), 7.85 (d, J = 8.2 Hz, 1H),7.49 (d, J = 5.4 Hz, 1H), 7.43 (dd, J = 8.2, 1.5 Hz, 1H), 7.36 (dd, J =5.5, 0.6 Hz, 1H), 4.84 (s, 2H), 3.96 (s, 3H), 2.19 (s, 3H) 3.19 157-162¹H NMR (400 MHz, DMSO-d₆) δ 8.11 (s, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.87(d, J = 5.5 Hz, 1H), 7.54 (d, J = 5.4 Hz, 1H), 7.46 (dd, J = 8.2, 1.5Hz, 1H), 6.86 (s, 2H), 2.12 (s, 3H) 3.20 143-145 ¹H NMR (DMSO-d₆) δ 3.76(s, 3H), 3.92 (s, 3H), 7.40 (s, 2H), 7.51 (d, J = 5.5 Hz, 1H), 7.88 (d,J = 5.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 8.26 (dd, J = 8.5, 1.5 Hz,1H), 8.79 (d, J = 1.1 Hz, 1H). 3.21 134-136 ¹H NMR (DMSO-d₆) δ 3.77 (s,3H), 7.32 (s, 1H), 7.51 (dd, J = 5.4, 0.8 Hz, 1H), 7.88 (d, J = 5.4 Hz,1H), 7.94 (d, J = 8.4 Hz, 1H), 8.28 (dd, J = 8.4, 1.5 Hz, 1H), 8.81-8.86(m, 1H). 3.22 168 ¹H NMR (400 MHz, CDCl₃) δ 8.44 (d, J = 6.8 Hz, 1H),7.58 (t, J = 4.0 Hz, 1H), 7.54-7.52 (m, 1H), 7.30 (d, J = 5.4 Hz, 1H),5.41 (s, 2H), 4.02 (s, 3H), 3.96 (s, 3H). 3.23 219-221 ¹H NMR (400 MHz,CDCl₃) δ 8.01 (d, J = 1.7 Hz, 1H), 7.85 (ddt, J = 9.5, 7.3, 3.6 Hz, 2H),7.43-7.33 (m, 2H), 4.93 (s, 2H), 4.02 (s, 3H) 3.24 121-123 ¹H NMR (400MHz, CDCl₃) δ 7.97-7.85 (m, 2H), 7.54 (d, J = 5.6 Hz, 1H), 7.47 (t, J =7.7 Hz, 1H), 7.39 (d, J = 5.6 Hz, 1H), 4.96 (s, 2H), 4.04 (s, 3H) 3.25183-185 ¹H NMR (300 MHz, DMSO-d₆) δ 8.00 (dd, J = 7.9, 0.8 Hz, 1H),7.87- 7.82 (m, 1H), 7.80 (d, J = 5.5 Hz, 1H), 7.56-7.50 (m, 2H), 6.97(s, 2H) 3.26 181-184 ¹H NMR (600 MHz, CDCl₃) δ 8.05 (d, J = 7.5 Hz, 1H),7.95 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H), 7.56 (s, 1H), 4.98(s, 2H), 4.05 (s, 3H) 3.27 ¹H NMR (400 MHz, DMSO-d₆) δ 7.96 (dd, J =7.8, 1.0 Hz, 1H), 7.76- 7.84 (m, 2H), 7.53 (d, J = 7.7 Hz, 1H),7.47-7.51 (m, 2H), 6.82 (s, 2H), 3.94 (s, 3H) 4.01 188-190 ¹H NMR (300MHz, CDCl₃) δ 10.09 (br s, 1H), 8.36 (s, 1H), 8.16 (s, 1H), 8.03 (dt, J= 9, 1.5 Hz, 1H), 7.57 (d, J = 9 Hz, 1H), 4.90 (br s, 2H), 4.00 (s, 3H)4.02 284-287 ¹H NMR (300 MHz, DMSO-d₆) δ 13.49 (br s, 1H), 13.19 (br s,1H), 8.28 (s, 1H), 8.21 (s, 1H), 7.89 (dt, J = 9, 1 Hz, 1H), 7.66 (dt, J= 9, 1 Hz, 1H), 6.82 (br s, 2H) 4.03 156-159 ¹H NMR (400 MHz, CDCl₃) δ8.34 (m, 1H), 8.07 (d, J = 1 Hz, 1H), 8.03 (dt, J = 9, 1.5 Hz, 1H), 7.47(dt, J = 9, 1 Hz, 1H), 4.89 (br s, 2H), 4.10 (s, 3H), 3.99 (s, 3H) 4.04186-188 ¹H NMR (400 MHz, DMSO-d₆) δ 13.53 (br s, 1H), 8.28 (s, 1H), 8.19(s, 1H), 7.92 (d, J = 9 Hz, 1H), 7.75 (d, J = 9 Hz, 1H), 6.81 (br s,2H), 4.10 (s, 3H) 4.05 185-187 ¹H NMR (400 MHz, DMSO-d₆) δ 13.21 (br s,1H), 8.16 (s, 1H), 8.01 (s, 1H), 7.88 (dd, J = 9, 1 Hz, 1H), 7.61 (dt, J= 9, 1.5 Hz, 1H), 6.96 (br s, 2H), 3.91 (s, 3H) 4.06 >300  ¹H NMR (400MHz, DMSO-d₆) δ 13.20 (br s, 1H), 8.15 (s, 1H), 8.03 (s, 1H), 7.87 (d, J= 9 Hz, 1H), 7.64 (dt, J = 9, 1.5 Hz, 1H), 6.66 (br s, 2H) 4.07 187-190¹H NMR (400 MHz, CDCl₃) δ 8.03 (d, J = 1 Hz, 1H), 8.00 (t, J = 1 Hz,1H), 7.82 (dd, J = 9, 1 Hz, 1H), 7.72 (m, 1H), 4.94 (br s, 2H), 4.15 (s,3H), 4.01 (s, 3H) 4.08 182-184 ¹H NMR (400 MHz, DMSO-d₆) δ 13.68 (br s,1H), 8.14 (d, J = 1 Hz, 1H), 8.06 (s, 1H), 7.89 (dd, J = 9, 0.5 Hz, 1H),7.62 (dt, J = 9, 1 Hz, 1H), 6.88 (br s, 2H), 4.13 (s, 3H) 4.09 191-193¹H NMR (400 MHz, DMSO-d₆) δ 13.19 (s, 1H), 8.08 (d, J = 21.7 Hz, 2H),7.84 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.38 (s, 1H), 6.76(s, 2H), 3.91 (s, 3H) 4.10 170-175 ¹H NMR (400 MHz, CDCl₃) δ 8.42 (s,1H), 7.63 (dt, J = 5.8, 2.2 Hz, 1H), 7.53-7.45 (m, 2H), 4.96 (s, 2H),4.12 (s, 3H), 4.01 (s, 3H) 4.11 173-175 ¹H NMR (400 MHz, DMSO-d₆) δ13.62 (s, 1H), 8.23 (s, 1H), 7.88-7.70 (m, 1H), 7.63-7.45 (m, 2H), 6.93(s, 2H), 4.11 (d, J = 10.3 Hz, 4H) 4.12 212-215 ¹H NMR (400 MHz, CDCl₃)δ 10.10 (s, 1H), 8.55 (s, 1H), 7.66 (dd, J = 7.2, 1.5 Hz, 1H), 7.59 (d,J = 8.4 Hz, 1H), 7.54-7.45 (m, 1H), 4.97 (s, 2H), 4.02 (s, 3H) 4.13207-210 ¹H NMR (400 MHz, CDCl₃) δ 12.67 (s, 1H), 8.23 (d, J = 7.5 Hz,1H), 8.15 (d, J = 1.9 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.29 (d, J =7.7 Hz, 1H), 5.02 (s, 2H), 4.12 (s, 3H) 5.01 ¹H NMR (400 MHz, CDCl₃) δ8.36 (d, J = 1.5 Hz, 1H), 8.16 (s, 1H), 8.06- 7.98 (m, 1H), 7.68 (d, J =8.6 Hz, 1H), 4.95 (s, 2H), 4.00 (s, 3H). 6.01 216 ¹H NMR (400 MHz,DMSO-d₆) δ 9.48 (s, 1H), 8.49 (s, 1H), 8.30 (d, J = 8.8 Hz, 1H), 7.95(d, J = 8.5 Hz, 1H), 6.99 (s, 2H), 3.91 (s, 3H) 6.02 186-187 ¹H NMR (400MHz, DMSO-d₆) δ 13.54 (s, 1H), 9.47 (s, 1H), 8.52 (s, 1H), 8.30 (d, J =8.5 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 6.91 (s, 2H) 7.01 219-221 ¹H NMR(300 MHz, DMSO-d₆) δ 8.31 (s, 1H), 8.04 (br s, 1H), 7.70 (br s, 2H),6.92 (br s, 2H), 3.89 (s, 3H) 7.02 218-220 ¹H NMR (300 MHz, DMSO-d₆) δ8.28 (s, 1H), 7.97 (br s, 1H), 7.75 (d, J = 9 Hz, 1H), 7.68 (dt, J = 9,1.5 Hz, 1H), 6.94 (br s, 2H), 3.90 (s, 6H) 7.03 230-235 ¹H NMR (300 MHz,DMSO-d₆) δ 8.76 (s, 1H), 8.13 (s, 1H), 7.83 (s, 2H), dec 6.92 (br s,2H), 3.98 (s, 3H) 8.01 ¹H NMR (400 MHz, DMSO-d₆) δ 8.10 (t, J = 9.8 Hz,1H), 7.89 (s, 1H), 7.70 (t, J = 8.2 Hz, 1H), 7.08 (s, 2H), 3.94-3.85 (m,3H), 3.16 (s, 6H) 9.01 129-33  ¹H NMR (400 MHz, DMSO-d6) δ) 15.84 (s,1H), 8.35 (s, 1H), 7.98 (s, 2H), 7.41 (s, 1H), 6.79 (s, 2H), 3.91 (s,3H).

TABLE 12 Percent Control Rating Conversion Table Rating % Control A 95-100 B 85-94 C 75-84 D 60-74 E 45-59 F 30-44 G  0-29

Example A Evaluation of Postemergent Herbicidal Activity

Post-emergent Test I Seeds test species were obtained from commercialsuppliers and planted into a 5″-round pot containing soil-less media mix(metro-mix 360®, Sun Gro Horticulture). Postemergence treatments wereplanted 8-12 days prior to application and cultured in a greenhouseequipped with supplemental light sources to provide a 16 h photoperiodat 24-29° C. All pots were surface irrigated.

Approximately 10 milligrams (mg) of each compound were dissolved in 1.3mL acetone-DMSO (97:3, v/v) and diluted with 4.1 mLwater-isopropanol-crop oil concentrate (78:20:2, v/v/v) containing 0.02%Triton X-155. Treatments were serial diluted with the above formulationsolvent to provide 1.85, 0.926, 0.462 and 0.231 mg/mL of test compounddelivered in 2.7 mL/pot (roughly equivalent to 4.0, 2.0, 1.0, and 0.5kg/ha, respectively).

Formulated compounds were applied using a DeVilbiss® compressed airsprayer at 2-4 psi. Following treatment, pots were returned to thegreenhouse for the duration of the experiment. All pots weresub-irrigated as need to provide optimum growing conditions. All potswere fertilized one time per week by subirrigating with Peters Peat-LiteSpecial® fertilizer (20-10-20).

Phytotoxicity ratings were obtained 10 days after treatmentpostemergence applications. All evaluations were made visually on ascale of 0 to 100 where 0 represents no activity and 100 representscomplete plant death. Visual assessments of plant injury were made basedon growth reduction, discoloration, leaf deformity and necrosis

Some of the compounds tested, application rates employed, plant speciestested, and results are given in Table 13.

TABLE 13 Post-emergent Test I Herbicidal Activity on Key Broadleaf andGrass Weed as well as Crop Species Com- Application Visual GrowthReduction (%) 10 Days After pound Rate (Kg Application Number ai/ha)AVEFA ECHCG HELAN IPOHE SETFA 1.10 3.96 G G A F G 1.48 4 G G C n/a G3.05 4 C A B B A AVEFA: wild oats (Avena fatua) ECHCG: barnyardgrass(Echinochloa crus-galli) HELAN: sunflower (Helianthus annuus) IPOHE:ivyleaf morningglory (Ipomoea hederecea) SETFA: giant foxtail (Setariafaberi) g ai/ha: grams active ingredient per hectare

Example B Evaluation of Preemergent Herbicidal Activity

Pre-emergent Test I Seeds of test species were planted into roundplastic pots (5-inch diameter) containing sandy loam soil. Afterplanting, all pots were sub-irrigated 16 h prior to compoundapplication.

Compounds were dissolved in a 97:3 v/v (volume/volume) mixture ofacetone and dimethyl sulfoxide (DMSO) and diluted to the appropriateconcentration in a final application solution containing water, acetone,isopropanol, DMSO and Agri-dex (crop oil concentrate) in a59:23:15:1.0:1.5 v/v ratio and 0.02% w/v (weight/volume) of Triton X-155to obtain the spray solution containing the highest application rate.The high application rate was serial diluted with the above applicationsolution to provide delivery of the compound at rates ½×, ¼× and ⅛× ofthe highest rate (equivalent to 4.0, 2.0, 1.0, and 0.5 kg/ha,respectively).

Formulated compound (2.7 mL) was applied pipetted evenly over the soilsurface followed by incorporation with water (15 mL). Followingtreatment, pots were returned to the greenhouse for the duration of theexperiment. The greenhouse was programmed for an approximate 15 hphotoperiod which was maintained at about 23-29° C. during the day and22-28° C. during the night. Nutrients and water were added on a regularbasis through surface irrigation and supplemental lighting was providedwith overhead metal halide 1000-Watt lamps as necessary.

Herbicidal effect ratings were obtained 14 days after treatment. Allevaluations were made relative to appropriate controls on a scale of 0to 100 where 0 represents no herbicidal effect and 100 represents plantdeath or lack of emergence from the soil. Some of the compounds tested,application rates employed, plant species tested, and results are givenin Table 14.

TABLE 14 Pre-emergent Test I Herbicidal Activity on Key Broadleaf andGrass Weed as well as Crop Species Com Application Visual GrowthReduction (%) 14 Days After pound Rate (Kg Application Number ai/ha)AVEFA ECHCG HELAN IPOHE SETFA 1.10 3.96 G F G G G 1.48 4 G G C D G 3.054 F A F A A AVEFA: wild oats (Avena fatua) ECHCG: barnyardgrass(Echinochloa crs-galli) HELAN: sunflower (Helianthus annuus) IPOHE:ivyleaf morningglory (Ipomoea hederecea) SETFA: giant foxtail (Setariafaberi) g ai/ha: grams active ingredient per hectare

Example C Evaluation of Postemergent Herbicidal Activity

Post-emergent Test II: Seeds or nutlets of the desired test plantspecies were planted in Sun Gro Metro-Mix® 360 planting mixture, whichtypically has a pH of 6.0 to 6.8 and an organic matter content of about30 percent, in plastic pots with a surface area of 64 squarecentimeters. When required to ensure good germination and healthyplants, a fungicide treatment and/or other chemical or physicaltreatment was applied. The plants were grown for 7-21 d in a greenhousewith an approximate 15 h photoperiod which was maintained at about23-29° C. during the day and 22-28° C. during the night. Nutrients andwater were added on a regular basis and supplemental lighting wasprovided with overhead metal halide 1000-Watt lamps as necessary. Theplants were employed for testing when they reached the first or secondtrue leaf stage.

A weighed amount, determined by the highest rate to be tested, of eachtest compound was placed in a 25 mL glass vial and was dissolved in 4 mLof a 97:3 v/v mixture of acetone and DMSO to obtain concentrated stocksolutions. If the test compound did not dissolve readily, the mixturewas warmed and/or sonicated. The concentrated stock solutions obtainedwere diluted with 20 mL of an aqueous mixture containing acetone, water,isopropyl alcohol, DMSO, Atplus 411F crop oil concentrate, and Triton®X-155 surfactant in a 48.5:39:10:1.5:1.0:0.02 v/v ratio to obtain spraysolutions containing the highest application rates. Additionalapplication rates were obtained by serial dilution of 12 mL of the highrate solution into a solution containing 2 mL of 97:3 v/v mixture ofacetone and DMSO and 10 mL of an aqueous mixture containing acetone,water, isopropyl alcohol, DMSO, Atplus 411F crop oil concentrate, andTriton X-155 surfactant in a 48.5:39:10:1.5:1.0:0.02 v/v ratio to obtain½×, ¼×, ⅛× and 1/16× rates of the high rate. Compound requirements arebased upon a 12 mL application volume at a rate of 187 liters perhectare (L/ha). Formulated compounds were applied to the plant materialwith an overhead Mandel track sprayer equipped with 8002E nozzlescalibrated to deliver 187 L/ha over an application area of 0.503 squaremeters at a spray height of 18 inches (43 cm) above the average plantcanopy height. Control plants were sprayed in the same manner with thesolvent blank.

The treated plants and control plants were placed in a greenhouse asdescribed above and watered by subirrigation to prevent wash-off of thetest compounds. After 14 d, the condition of the test plants as comparedwith that of the untreated plants was determined visually and scored ona scale of 0 to 100 percent where 0 corresponds to no injury and 100corresponds to complete kill. Some of the compounds tested, applicationrates employed, plant species tested, and results are given in Tables 15and 16.

TABLE 15 Post-emergent Test II Herbicidal Activity on Key Broadleaf Weedand Crop Species Application Rate (g Visual Growth Reduction (%) 14 DaysAfter Application C. No. ai/ha) ABUTH AMARE BRSNN CHEAL EPHHL HELAN 1.0135 G n/a G G A G 70 G G G G A C 140 F E G G A C 1.02 35 G n/a G C E E 70G B G B E D 140 G B G A D D 1.03 35 G n/a G B A G 70 G n/a G B A G 140 CB G A B E 1.04 35 E D F E A E 70 G D E D A E 140 G D E D A B 1.05 35 E DF B F A 70 A C E A F A 140 B A D A E A 1.06 35 G A C B G G 70 G B B A GG 140 G C B A G G 1.07 35 G B G B D A 70 G A G B D A 140 G A G B D A1.08 35 B A E A A B 70 A A C A A A 140 A A B A A A 1.09 35 A A A A B A70 A A A A A A 140 A A A A A A 1.10 35 G G G A G G 70 G B G A G G 140 GA G A G E 1.13 35 G G G D G E 70 G F G C G D 140 G F F B F D 1.14 35 G CE D G D 70 G B D D G C 140 G B C C D C 1.15 35 A A C A A A 70 A A A A AA 140 A A A A A A 1.16 35 B A A A A A 70 A A A A A A 140 A A A A A B1.17 35 E A A A A A 70 E A A A A A 140 D A A A A A 1.19 35 A A A A A D70 A A A A A C 140 A A A A A A 1.20 35 E C A A A A 70 D B A A A A 140 DA A A A A 1.21 35 D G G E C E 70 D G G B B C 140 D E D B A C 140 G G G GG G 1.22 35 G C E G E C 70 G C D G C B 140 G B D G B B 1.23 35 A A D A AD 70 A A C A A C 140 A A B A A B 1.24 35 B A B B A D 70 A A E A A C 140A A A A A B 1.25 35 G C D G G G 70 G B C D G G 140 F A B D F G 1.26 35 GC B G G G 70 G B A F F G 140 G A A F E G 1.27 35 D D B B A G 70 B A A BA G 140 B A A B A G 1.28 35 B G C E G A 70 B G B D G A 140 A D B D G A1.29 35 G E C E G D 70 G G C E G D 140 G G B C G C 1.30 35 G G E F G G70 G C E F E G 140 C D D E D G 1.31 35 E D B A A F 70 D A A A A E 140 DA A A A D 1.32 35 G G F G G E 70 G F E G D D 140 G D D C B C 1.33 35 G DA G E D 70 G D A E D D 140 G C A D C C 1.34 35 G G C G G B 70 G G B E GA 140 G F A D D A 1.35 35 G C A G C F 70 G B A G C D 140 G A A B B A1.37 35 G G F G G G 70 G G D G G G 140 G G C G G G 1.39 35 G A C A B G70 G A B C C G 1.40 35 G n/a G G G G 70 G A G G G F 140 G n/a G G G E1.43 35 G A G C G D 70 G A G B G C 140 D A G B F C 1.44 35 G B G B E G70 C A G B C G 140 B A F A B G 1.45 35 G G G G G G 70 G G G G G G 140 GE G G G F 1.46 35 G G G C G G 70 G G G B G F 140 G D G A G E 1.47 35 G GG C G G 70 G G G C G G 140 G F G B G E 1.48 140 G G G D G C 1.49 35 B GG B G G 70 B F G B G G 140 B G G A G E 2.02 35 E C G A C C 70 B A F A AB 140 B A F A A A 2.03 35 A D G B E G 70 A B G A C D 140 A B G A C C 280A A F A B B 2.04 35 C A G A A G 70 B A G A A G 140 A A F A A F 2.05 35 GB G G F G 70 G C G G F G 140 G A G E E F 2.06 35 G C F D F D 70 G A D CC C 140 C A B B A B 2.09 35 B B D A A D 70 B A C A A C 140 B A B A A B2.10 35 D B F B A C 70 D A D A A B 140 B A C B A A 2.11 35 A A C A A E70 A A B A A D 140 A A A A A C 2.12 35 B A C A A F 70 A A B A A D 140 AA A A A D 2.13 35 A D A A A C 70 A A A A A B 140 A A A A A A 2.14 35 G AA B B D 70 G A A A A B 140 G A A A A A 2.15 35 E A E A G E 70 C A C A GC 140 A A B A G C 2.16 35 B A E A G A 70 A A D A G A 140 A A D A G A2.17 140 C A C A A B 2.18 35 G A E B G C 70 G A D B G C 140 G A D B G B2.19 35 A A G A G G 70 A A D A G C 140 A A D A G C 2.20 35 E A G B G B70 D A G A G A 140 D A F A G A 2.21 35 F A F B G D 70 D A F B G C 140 DA E A G C 2.22 35 F A G A G C 70 F A E A G B 140 E A D A G A 2.23 35 G AG A G B 70 G A G A G A 140 G A G A G A 2.24 35 C A D A D C 70 C A C A CC 140 A A C A C B 2.25 35 C A G A G G 70 C A E A C F 140 A A C A B B2.26 35 E A E A E C 70 D A D A D A 140 D A D A C A 3.01 35 D B G A G C70 D A G A G C 140 C A G A G B 3.02 35 G A G B G D 70 G A G B G C 140 GA G B G B 3.03 35 A A G A A A 70 A A D A A A 140 A A D A A A 3.05 35 B FG C D G 70 B E G B D G 140 A D G B C F 140 E A A A G B 280 A B G B B E3.06 35 E B F F G A 70 D B F D G A 140 B A E D F A 3.07 35 G G E G G B70 G D D G G B 140 G C D C G B 3.08 35 G G G B D D 70 F F G B C C 140 FD F B B B 3.09 35 G F E B A D 70 G C B B A C 140 E B A A A B 3.10 35 G AG C G B 70 G A G C G B 140 G A G C G B 3.11 35 G n/a G B G B 70 G n/a GB G B 140 G n/a G B G B 3.12 35 D D G A D B 70 A D G A D B 140 A B F A BB 3.13 35 G A G B G B 70 G A G A G B 140 C A D A D B 3.14 35 G B G B F B70 G A G B F B 140 G A G A D A 3.15 35 B A F B C D 70 A A E B C D 140 AA E A B B 3.16 35 D B G B D G 70 D A G B D G 140 C B E B D G 3.17 35 G CG B E G 70 E A G A D G 140 D A D A C F 3.18 35 D D G F E A 70 C C G D GA 140 C A G D F A 3.19 35 G D G D G B 70 G A G D G B 140 D C G C G B3.20 35 G G F B C C 70 G D D A A B 140 G D D A A B 3.21 35 G A C B C D70 F A B B B D 140 E A A A A C 3.22 35 G D G D A C 70 G A F C A B 140 GA D B A B 3.23 35 G G G G G G 70 G G G E G G 140 G G G B G G 3.24 35 G BE B G D 70 G B E A G D 140 G A E A G B 3.25 140 G A C A G E 3.27 35 G BE C G E 70 G A D B G D 140 E A D A G C 280 C A B A G B 4.01 35 G G G G GG 70 G E G D G G 140 G D G D G G 4.03 35 G G G A E G 70 G E G A D E 140G C G A C D 4.05 35 G G G B D D 70 G A G B A D 140 E A E A A A 4.06 35 GC D G E E 70 G A C E D D 140 G A B A B C 4.07 140 E n/a E G D A 4.08 140G n/a D A G B 4.09 35 G G G E G G 70 G E G C G F 140 G B D B G E 4.10 35G G G G G G 70 G A G G G G 140 G A G G G E 4.13 35 G n/a G G G G 70 Gn/a G G G G 140 G n/a G D G G 5.01 35 D C B D n/a B 70 D B A B A B 140 DB A B n/a A 6.01 35 B B A A G B 70 B A A A B B 140 B A A A A B 6.02 35 BA A A A A 70 B A A A A A 140 B A A A A A 7.02 35 G G G G G G 70 G G G CG G 140 G G G A G G 8.01 35 G G G G G G 70 G G G G G G 70 A E G B A A140 G G G G G G 140 A D G A A A ABUTH: velvetleaf (Abutilon theophrasti)AMARE: redroot pigweed (Amaranthus retroflexus) BRSNN: oilseed rape,canola (Brassica napus) CHEAL: lambsquarters (Chenopodium album) EPHHL:wild poinsettia (Euphorbia heterophylla) HELAN: sunflower (Helianthusannuus) g ai/ha: grams active ingredient per hectare

TABLE 16 Post-emergent Test II Herbicidal Activity on Key Grass andSedge Weeds as well as Grass Crops Application Rate (g Visual GrowthReduction (%) 14 Days After Application C. No. ai/ha) CYPES ECHCG SETFAORYSA TRZAS ZEAMX 1.01 35 G G G G G G 70 G n/a G G G A 140 G C G G G B1.02 35 G G G G G G 70 G G G G G G 140 G E G G G G 1.03 35 G G G G G G70 G G G G G G 140 G D G G G G 1.04 35 G G G G G G 70 G n/a G G G G 140G B G G G G 1.05 35 G G F G G G 70 G G E G F F 140 G D D G E E 106 35 GG G G G G 70 G D G G G G 140 G C G G G G 1.07 35 G G D G G G 70 G G C GG G 140 G G C G G G 1.08 35 G B G G G E 70 G A D G G C 140 G A C G F B1.09 35 F A B G G D 70 C A B G G C 140 B A B G G C 1.10 35 G G G G G G70 G G G G G G 140 G G G G G G 1.12 35 G G C G E G 70 G G D G G G 140 GB C G G G 1.13 35 G G G G G G 70 G G G G G G 140 G G G G G G 1.14 35 G GG G G G 70 G G G G G G 140 G G G G G G 1.15 35 G C D G E G 70 D B D G DF 140 E A B F D D 1.16 35 G C D F F G 70 D B C D D F 140 B A B D D D1.17 35 E B C G D D 70 E B B G D C 140 E B B G D C 1.19 35 B B D F D D70 C B C E C D 140 A A B D C B 1.20 35 G G E G G F 70 G D C G E E 140 GC B G D D 1.21 35 G G n/a G G G 70 G G n/a G G G 140 G G n/a G G G 140 GC G G G G 1.22 35 G G G G G G 70 G G D G G G 140 G G B G G G 1.23 35 G GG G G G 70 G G G G G G 140 G D D G F G 1.24 35 G G G G G G 70 G G E G FG 140 G G D G E G 1.25 35 G G G G G G 70 G G G G G G 140 G G G G G G1.26 35 G G G G G G 70 G G G G G G 140 G G G G G G 1.27 35 G G G G G G70 G G G G G G 140 G G G G G G 1.28 35 G G G G G G 70 G G G G F G 140 GG G G F G 1.29 35 G G G G G G 70 G G G G G G 140 F G G G G G 1.30 35 G GG G G G 70 G G G G G G 140 G G G G G G 1.31 35 G C D G C G 70 G C C G GG 140 G B B G F G 1.32 35 G G G G G G 70 G G G G G G 140 G G G G G G1.33 35 G G G G G n/a 70 G G G G G n/a 140 G G G G F n/a 1.34 35 G G G GG G 70 G G G G G G 140 G G D G F G 1.35 35 G G G G G G 70 G G G G F G140 G G G G E G 1.37 35 G G G G G G 70 G G G G G G 140 G G G G G G 1.3935 G G G G G G 70 G G G G G G 1.40 35 G G G G G G 70 G G G G G G 140 G GG G G G 1.43 35 G G G G G G 70 G G G G G G 140 G G G G G G 1.44 35 G G GG G G 70 G G G G G G 140 G G G G G G 1.45 35 G G G G G G 70 G G G G G G140 G G G G G G 1.46 35 G G G G G G 70 G G G G G G 140 G G G G G G 1.4735 G G G G G G 70 G G G G G G 140 G G G G G G 1.48 140 G G G G G G 35 GG G G G G 70 G G G G G G 140 G G G G G G 2.02 35 G B D G G A 70 G B D GF A 140 G A C G E A 2.03 35 G F G G G G 70 G D G G G G 140 G B F G G G280 G A F G G D 2.04 35 G D D G G D 70 G A C G F C 140 F A B G E B 2.0535 G G G G G G 70 G G G G G G 140 G G G G G G 2.06 35 G G G G G G 70 G EG G G G 140 G A G G G G 2.08 35 G B E G G E 70 G B D F G D 140 G A B F GD 2.09 35 G D E G G E 70 G B D F G D 140 G B D F G D 2.10 35 G D D G G G70 G D D F F F 140 F B C F D E 2.11 35 G B E G G E 70 G A D G G D 140 FA C G F B 2.12 35 G A E G G G 70 G A D G G F 140 G A D G G D 2.13 35 F CG G G G 70 B A E F E F 140 B A D F E E 2.14 35 G G G G G G 70 G G G G GG 140 G C G G G G 2.15 35 G G G G G A 70 G E G G G A 140 G C G G G A2.16 35 G G G G G E 70 G G G G G A 140 G G G G G A 2.17 140 A C G G G F2.18 35 G G G G G G 70 G G G G G G 140 G G G G G G 2.19 35 G G n/a G G G70 G G n/a G G G 140 G G n/a G G G 2.20 35 G n/a G G G G 70 G n/a F G GG 140 G n/a D G G G 2.21 35 G n/a G G G G 70 G n/a G G G G 140 G n/a G GG G 2.22 35 G G G G G G 70 G G G G G G 140 G G G G G G 2.23 35 G G G G GG 70 G G G G G G 140 G G G G G G 2.24 35 D G G G G G 70 C G G G G F 140B G G G G D 2.25 35 G G G G G G 70 F G G G G G 140 C G G G G E 2.26 35 GG G G G G 70 G G G G G G 140 G G G G G G 3.01 35 G G G G G G 70 G G G GG E 140 G G G G G D 3.02 35 G G G G G G 70 G G G G G D 140 G G G G G D3.03 35 E B G G G A 70 E A B G F A 140 E A B G E A 3.05 35 G E G G G G70 G C G G G G 140 G B F G G E 280 G B D G G D 3.06 35 G G G G G G 70 GG G G G G 140 G G G G G G 3.07 35 G G G G G G 70 G G G G G G 140 G G G GG G 3.08 35 G G G G E F 70 G G G G D D 140 F C G G D C 3.09 35 G B G G DD 70 G B G G C C 140 G B G G B B 3.10 35 G G G G G D 70 G G G G G D 140G G G G G D 3.11 35 G G G G G G 70 G G G G G G 140 G G G G G G 3.12 35 GB G G G A 70 G B G G G A 140 G B G G G A 3.13 35 G D n/a G G D 70 G Dn/a G G D 140 G C n/a G G D 3.14 35 G G G G G G 70 G G G G G F 140 G G GG G D 3.15 35 G C G G G D 70 G C G G G D 140 G A G G G D 3.16 35 G C G GG D 70 G C G G G D 140 E C G G G C 3.17 35 G E G G G F 70 G D G G G D140 G A F G G C 3.18 35 G G G G G G 70 G G G G G G 140 G G G G G G 3.1935 G G G G G G 70 G G G G G G 140 G G G G G G 3.20 35 F G G G G G 70 F EG G G C 140 B D D G F B 3.21 35 G C G G F F 70 G B F F F D 140 G B D F EC 3.22 35 G G G G G G 70 G G G G G G 140 G G G G G G 3.23 35 G G G G G G70 G G G G G G 140 G G G G G G 3.24 35 G G G G G G 70 G G G G G G 140 GG G G G G 3.25 140 G G G G G G 3.27 35 G G G G G G 70 G G G G G G 140 GG G G G G 280 G G G G G G 4.01 35 G G G G G G 70 G G G G G G 140 G G G GG G 4.03 35 G D n/a G G G 70 G C n/a G G G 140 G C n/a G G G 4.05 35 Gn/a n/a G G G 70 G n/a n/a G G D 140 G B A G G D 4.06 35 G G G G G G 70G E G G G G 140 G C E G G G 4.07 140 G G G G G G 4.08 140 G G G G G G4.09 35 G G G G G G 70 G G G G G G 140 G G G G G G 4.10 35 G G G G G G70 G G G G G G 140 G G G G G G 4.13 35 G G G G G G 70 G G G G G G 140 GG G G G G 5.01 35 n/a C G G G G 70 n/a C G G G G 140 n/a B G G G G 6.0135 E G G G G G 70 E E G G G G 140 E D G G G G 6.02 35 E C G G G G 70 E CE G G G 140 E B D G F G 7.02 35 G G n/a G G G 70 G G n/a G G G 140 G Gn/a G G G 8.01 35 G G G G G G 70 G G G G G G 140 G G G G G G 9.01 140 AA G G G D ECHCG: barnyardgrass (Echinochloa crus-galli) CYPES: yellownutsedge (Cyperus esculentus) ORYSA: rice (Oryza sativa) SETFA: giantfoxtail (Setaria faberi) TRZAS: wheat, spring (Triticum aestivum) ZEAMX:maize, corn (Zea mays) g ai/ha: grams active ingredient per hectare

Example D Evaluation of Postemergent Herbicidal Activity in Wheat andBarley

Post-emergent Test III. Seeds of the desired test plant species wereplanted in Sun Gro MetroMix® 306 planting mixture, which typically has apH of 6.0 to 6.8 and an organic matter content of about 30 percent, inplastic pots with a surface area of 103.2 square centimeters (cm²). Whenrequired to ensure good germination and healthy plants, a fungicidetreatment and/or other chemical or physical treatment was applied. Theplants were grown for 7-36 days (d) in a greenhouse with an approximate14 hour (h) photoperiod which was maintained at about 18° C. during theday and 17° C. during the night. Nutrients and water were added on aregular basis and supplemental lighting was provided with overhead metalhalide 1000-Watt lamps as necessary. The plants were employed fortesting when they reached the second or third true leaf stage.

A weighed amount, determined by the highest rate to be tested, of eachtest compound was placed in a 25 mL glass vial and was dissolved in 4 mLof a 97:3 v/v mixture of acetone and DMSO to obtain concentrated stocksolutions. If the test compound did not dissolve readily, the mixturewas warmed and/or sonicated. The concentrated stock solutions obtainedwere diluted with 20 mL of an aqueous mixture containing acetone, water,isopropyl alcohol, DMSO, Agri-Dex crop oil concentrate, and X-77surfactant in a 48:39:10:1.5:1.5:0.02 v/v ratio to obtain spraysolutions containing the highest application rates. Additionalapplication rates were obtained by serial dilution of 12 mL of the highrate solution into a solution containing 2 mL of 97:3 v/v mixture ofacetone and DMSO and 10 mL of an aqueous mixture containing acetone,water, isopropyl alcohol, DMSO, Agri-Dex crop oil concentrate, and X-77surfactant in a 48:39:10:1.5:1.5:0.02 v/v ratio to obtain ½×, ¼×, ⅛× and1/16× rates of the high rate. Compound requirements are based upon a 12mL application volume at a rate of 187 liters per hectare (L/ha).Formulated compounds were applied to the plant material with an overheadMandel track sprayer equipped with 8002E nozzles calibrated to deliver187 L/ha over an application area of 0.503 square meters at a sprayheight of 18 inches (43 cm) above the average plant canopy height.Control plants were sprayed in the same manner with the solvent blank.

The treated plants and control plants were placed in a greenhouse asdescribed above and watered by subirrigation to prevent wash-off of thetest compounds. After 21 d, the condition of the test plants as comparedwith that of the untreated plants was determined visually and scored ona scale of 0 to 100 percent where 0 corresponds to no injury and 100corresponds to complete kill. By applying the well-accepted probitanalysis as described by J. Berkson in Journal of the AmericanStatistical Society, 48, 565 (1953) and by D. Finney in “ProbitAnalysis” Cambridge University Press (1952), the above data can be usedto calculate GR₂₀, GR₅₀, GR₈₀ and GR₉₀ values, which are defined asgrowth reduction factors that correspond to the effective dose ofherbicide required to kill or control 20 percent, 50 percent, 80 percentor 90 percent, respectively, of a target plant.

Some of the compounds tested, application rates employed, plant speciestested, and results are given in Table 17.

TABLE 17 Activity of Herbicidal Compounds in Wheat and Barley Appli-Com- cation pound Rate (g Visual Growth Reduction (%) 21 Days AfterApplication No. ai/ha) HORVS TRZAS CIRAR GALAP KCHSC LAMPU MATCH PAPRHSASKR SINAR VERPE VIOTR 1.15 17.5 F F F D D A F A C A A E 35 E E D B B AE A C A A D 70 E D C A B A D A B A A C GR20  8 13 — — — — — — — — — —GR50 — — 30  9  6   0.10 45   0.06  7  4   0.28 22 GR80 — — 70 23 281 >140  1 30  8 2 63 GR90 — — 109  37 67 2 >140  2 95 12 6 111  1.1617.5 G G D F C C B A D B A E 35 G G B E B A A A C A A D 70 F F A A A A AA B A A C GR20 44 41 — — — — — — — — — — GR50 — —  9 26  7 3  3    0.0004 10  5    0.0004 19 GR80 — — 25 34 20 10   9     0.0004 28 11  0.05 56 GR90 — — 43 40 39 19  16     0.0004 78 17 1 99 1.23 17.5 G G GA F B G D F C B G 35 G G G A E A G A E C B E 70 G G G A D A G A C A A DGR20 >140  66 — — — — — — — — — — GR50 — — >140   1 35 3 0 11 29  3 1 44GR80 — — >140   4 110  6 0 17 90 14 8 119  GR90 — — >140   7 >140  9 022 >140  32 21  >140  2.24 17.5 G G D D D E G D D B F E 35 G G C B C D GD B A D D 70 G F B B B C G C B A C C GR20 66 52 — — — — — — — — — — GR50— — 14  7  4 15  114  24  3  6 30  24 GR80 — — 35 23 33 93  >140  52 2813 66  78 GR90 — — 57 44 103  >140   >140  77 95 19 100  >140 

1-32. (canceled)
 33. A compound of the Formula (I):

wherein X is N or CY, wherein Y is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkoxy, C₁-C₃ alkylthio, or C₁-C₃ haloalkylthio; R¹ is OR^(1′) or NR^(1″)R^(1″′), wherein R^(1′) is hydrogen, C₁-C₈ alkyl, or C₇-C₁₀ arylalkyl, and R^(1″) and R^(1″′) are independently hydrogen, C₁-C₁₂ alkyl, C₃-C₁₂ alkenyl, or C₃-C₁₂ alkynyl; R² is halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₁-C₄ alkylthio, C₁-C₄ haloalkylthio, amino, C₁-C₄ alkylamino, C₂-C₄ haloalkylamino, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, cyano, or a group of the formula —CR¹⁷═CR¹⁸—SiR¹⁹R²⁰R²¹, wherein R¹⁷ is hydrogen, F, or Cl; R¹⁸ is hydrogen, F, Cl, C₁-C₄ alkyl, or C₁-C₄ haloalkyl; and R¹⁹, R²⁰, and R²¹ are independently C₁-C₁₀ alkyl, C₃-C₆ cycloalkyl, phenyl, substituted phenyl, C₁-C₁₀ alkoxy, or OH; R³ and R⁴ are independently hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alkynyl, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkylcarbamyl, C₁-C₆ alkylsulfonyl, C₁-C₆ trialkylsilyl, C₁-C₆ dialkylphosphonyl, or R³ and R⁴ taken together with N is a 5- or 6-membered saturated ring, or R³ and R⁴ taken together represent ═CR^(3′)(R^(4′)), wherein R^(3′) and R^(4′) are independently hydrogen, C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, C₁-C₆ alkoxy or C₁-C₆ alkylamino, or, R^(3′) and R^(4′) taken together with ═C represent a 5- or 6-membered saturated ring; A is A3 or A15

R⁵ is hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino, C₂-C₄ haloalkylamino, OH, or CN; R⁶, R^(6′), and R^(6″) are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino or C₂-C₄ haloalkylamino, OH, CN, or NO₂; R⁷ and R^(7′) are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy,C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino, C₂-C₄ haloalkylamino, or phenyl; R⁸ is hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alkynyl, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkylcarbamyl, C₁-C₆ alkylsulfonyl, C₁-C₆ trialkylsilyl, or phenyl; or an N-oxide or agriculturally acceptable salt thereof.
 34. The compound of claim 33, wherein X is N or CY, wherein Y is hydrogen or halogen; R¹ is OR^(1′), wherein R^(1′) is hydrogen, C₁-C₈ alkyl, or C₇-C₁₀ arylalkyl; R² is halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₄-alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₄-alkoxy, C₁-C₄ haloalkoxy, C₁-C₄ alkylthio, or C₁-C₄ haloalkylthio. R³ and R⁴ are hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alkynyl, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, or R³ and R⁴ taken together represent ═CR^(3′)(R^(4′)), wherein R^(3′) and R^(4′) are independently hydrogen, C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, C₁-C₆ alkoxy or C₁-C₆ alkylamino; R⁵ is hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, C₁-C₃ haloalkylthio, amino, C₁-C₄ alkylamino, or C₂-C₄ haloalkylamino; R⁶, R^(6′), and R^(6″) are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, cyclopropyl, halocyclopropyl, C₂-C₄ alkenyl, C₂-C₄ haloalkenyl, C₂-C₄ alkynyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, CN, or NO₂; R⁷ and R^(7′) are independently hydrogen, halogen, C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, C₁-C₃ alkylthio, cyclopropyl, amino or C₁-C₄ alkylamino; R⁸ is hydrogen, C₁-C₆ alkyl, C₁-C₄ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, formyl, C₁-C₃ alkylcarbonyl, C₁-C₃ haloalkylcarbonyl, C₁-C₆ alkoxycarbonyl, or C₁-C₆ alkylcarbamyl.
 35. The compound of claim 34, wherein X is CF, CCl, or CBr.
 36. The compound of claim 35, wherein X is CY, wherein Y is CF.
 37. The compound of claim 35, wherein X is CY, wherein Y is CCl.
 38. The compound of claim 35, wherein X is CY, wherein Y is CBr.
 39. The compound of claim 34, wherein R² is Cl, methoxy, vinyl, or 1-propenyl.
 40. The compound of claim 34, wherein R³ and R⁴ are hydrogen.
 41. The compound of claim 34, wherein A is A3.
 42. The compound of claim 34, wherein A is A15.
 43. The compound of claim 34, wherein R⁵ is hydrogen or F.
 44. The compound of claim 43, wherein R⁵ is F.
 45. The compound of claim 34, wherein R⁶ is hydrogen or F.
 46. The compound of claim 34, wherein R⁶, R^(6′), R^(6″), R⁷, and R^(7′) are all hydrogen.
 47. A herbicidal composition comprising a compound of claim 33 and an agriculturally acceptable adjuvant or carrier.
 48. The composition of claim 47, further comprising an additional component selected from the group consisting of an insecticide, a herbicide, a fungicide, a safener, a growth regulator, or a combination thereof.
 49. The composition of claim 47, further comprising a herbicide selected from 2.4-D, 2,4-DB, MCPA, dichlorprop, mecoprop, dicamba, clopyralid, fluroxypyr, aminocyclopyrachlor, aminopyralid, or quinclorac.
 50. The composition of claim 47, further comprising a herbicide selected from ametridione, ametryn, amibuzin, anisuron, atraton, atrazine, bentazon-sodium, benzthiazuron, bromobonil, bromofenoxim, bromoxynil, buturon, chlorazine, chlorbromuron, chloreturon, chlorotoluron, chloroxuron, chloroxynil, cumyluron, cyanatryn, cyanazine, cycluron, cyprazine, daimuron, desmetryn, dichloralurea, difenoxuron, dimefuron, dimethametryn, dipropetryn, diuron, eglinazine, ethidimuron, fenuron, fluothiuron, hexazinone, ioxynil, ipazine, isoproturon, isouron, linuron, mesoprazine, metamitron, methabenzthiazuron, methiuron, methometon, methoprotryne, methyldymron, metobenzuron, metobromuron, metoxuron, metribuzin, monisouron, monolinuron, monuron, neburon, noruron, phenobenzuron, procyazine, proglinazine, prometon, prometryn, propazine, pyraclonil, sebuthylazine, secbumeton, simazine, simeton, simetryn, tebuthiuron, terbumeton, terbuthylazine, terbutryn, tetrafluoron, thiazafluoron, thidiazuron, triaziflam, or trietazine
 51. The composition of claim 47, further comprising a herbicide selected from amidosulfuron, azimsulfuron, bensulfuron-methyl, bispyribac-sodium, chlorimuron, chlorsulfuron, cinosulfuron, cloransulam-methyl, cyclosulfamuron, diclosulam, ethametsulfuron, ethoxysulfuron, flazasulfuron, florasulam, flucarbazone, flucetosulfuron, flumetsulam, flupyrsulfuron, foramsulfuron, halosulfuron-methyl, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, iodosulfuron, iofensulfuron, mesosulfuron, metazosulfuron, metosulam, metsulfuron, nicosulfuron, orthosulfamuron, oxasulfuron, penoxsulam, primisulfuron-methyl, propoxycarbazone, propyrisulfuron, prosulfuron, pyrazosulfuron-ethyl, pyribenzoxim, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac-methyl, pyroxsulam, rimsulfuron, sulfometuron, sulfosulfuron, thiencarbazone-methyl, thifensulfuron, triasulfuron, tribenuron, trifloxysulfuron, or tritosulfuron.
 52. The composition of claim 47, further comprising a safener selected from mefenpyrdiethyl, isoxadifen-ethyl, cloquintocet-mexyl, or dichlormid
 53. A method of controlling undesirable vegetation comprising applying to vegetation or an area adjacent the vegetation or applying to soil or water to control the emergence or growth of vegetation a herbicidally effective amount of a compound of claim
 33. 